DOSING & ADMINISTRATION for DARZALEX® (Daratumumab)

DR d

APRIL DVT d 2020 DVMP DV d DP d MONOTHERAPY

DOSING & IMPORTANT SAFETY ADMINISTRATION INFORMATION FOR DARZALEX® (daratumumab) ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing CHECKLIST Information. DR d Indications and mechanisms of action1 How DARZALEX® is supplied

® DVT d DARZALEX (daratumumab) is indicated for the Dosage form and strengths1 treatment of adult patients with multiple myeloma:

• in combination with lenalidomide and dexamethasone ®

DARZALEX is a colorless to pale yellow, DVMP in newly diagnosed patients who are ineligible for preservative-free solution for intravenous (IV) infusion. autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have • DARZALEX ® is supplied in single-use vials received at least one prior therapy DV d • in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant

• in combination with bortezomib, thalidomide, and DP d dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant 100 mg/5 mL 400 mg/20 mL • in combination with bortezomib and dexamethasone (20 mg/mL) (20 mg/mL) MONOTHERAPY in patients who have received at least one prior therapy • in combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies 1 including lenalidomide and a proteasome inhibitor 1Storage • as monotherapy, in patients who have received

at least three prior lines of therapy including a • Store in a refrigerator at 2°C to 8°C (36°F to 46°F) IMPORTANT SAFETY proteasome inhibitor (PI) and an immunomodulatory INFORMATION • Do not freeze or shake. Protect from light. This agent or who are double-refractory to a PI and an product contains no preservative immunomodulatory agent DARZALEX® is a first-in-class monoclonal antibody that targets CD381

• CD38 is expressed on hematopoietic cells, other cell Select Important Safety Information ADMINISTRATION types and tissues, and is highly expressed on multiple ® myeloma cells1,2 Neutropenia and Thrombocytopenia – DARZALEX may increase neutropenia and/or thrombocytopenia induced ® • DARZALEX inhibits tumor cell growth through immune- by background therapy. Monitor complete blood cell mediated, direct on-tumor, and immunomodulatory counts periodically during treatment according to the ® actions. DARZALEX may also have an effect on manufacturer’s prescribing information for background

1 INFUSION RATES normal cells therapies. Monitor patients with neutropenia for signs of & REACTIONS infection. DARZALEX® dose delay may be required to Important Safety Information allow recovery of neutrophils and/or platelets. No dose reduction of DARZALEX® is recommended. Consider CONTRAINDICATIONS supportive care with growth factors for neutropenia or DARZALEX® (daratumumab) is contraindicated in patients

transfusions for thrombocytopenia. PRE-/POST-INFUSION

with a history of severe hypersensitivity (eg, anaphylactic MEDICATIONS reactions) to daratumumab or any of the components of the formulation. WARNINGS AND PRECAUTIONS Please see additional Important Safety Information Infusion Reactions – DARZALEX® can cause severe throughout and on pages and/or serious infusion reactions, including anaphylactic

46-49, and click here for CHECKLIST reactions. In clinical trials, approximately half of all DARZALEX® full Prescribing patients experienced an infusion reaction. Information. 3 DR d Notes: DVT d DVMP DV d DP d MONOTHERAPY

DARZALEX® (daratumumab) + lenalidomide + IMPORTANT SAFETY

dexamethasone (DRd) INFORMATION DOSING & SAFETY

for adult patients with newly diagnosed, transplant-ineligible multiple myeloma ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 and click here for CHECKLIST DARZALEX® full Prescribing Information. DR

® d DARZALEX (daratumumab) DARZALEX® + Rd dosing schedule for adult patients with newly diagnosed, + Rd dosing

transplant-ineligible multiple myeloma DVT d In adult patients with newly diagnosed, DARZALEX® dosing frequency decreases over time1 transplant-ineligible multiple myeloma1 DVMP Dosing schedule based on a phase 3, randomized,

active-controlled trial

oto t e eoe DV d eetsoe s oe

§The first prescribed 16 mg/kg dose at Week 1 may be split over 2 consecutive days. See page 54 for details.

Recommended dosage DP d and schedule for DARZALEX®1

Doses given as 1 weekly infusion

Per (Cycles 1* to 2; Weeks 1 to 8) MONOTHERAPY 4 Cycle

Doses given as 1 infusion every 2 weeks Per (twice per 4-week cycle; Cycles 3 to 6; 2 Cycle Weeks 9 to 24) Cycle 7 onward (each lasting 28 days) Cycle 7 onward (each lasting 28 days) IMPORTANT SAFETY

Cycle 7 onward (each lasting 28 days) INFORMATION Dose given as 1 infusion every 4 weeks Cycle 7 onward (each lasting 28 days) Per (Cycle 7+; Week 25+ until disease 1 Cycle progression)

estimated Year 1 infusion visits 23 ADMINISTRATION See table on page 7 ▶ • Revlimid ® (lenalidomide) 25 mg is given orally on Days 1–21 of each cycle† • Dexamethasone 40 mg is given orally or IV Infusion reactions of any grade or severity may be managed by interruption, modification, and/or discontinuation

® INFUSION RATES once a week‡ of the infusion. DARZALEX should be permanently discontinued upon the third occurrence of a Grade 3 infusion & REACTIONS reaction and upon any occurrence of a Grade 4 infusion reaction. — On DARZALEX® infusion days, the entire ® dexamethasone dose was given as a No dose reductions of DARZALEX are recommended. Dose delay may be required to allow recovery of blood cell counts in the event of hematological toxicity [see Warnings and Precautions (5.3, 5.4)]. For information concerning pre-infusion medication drugs given in combination with DARZALEX®, see manufacturer’s prescribing information.

Revlimid® is a registered trademark of Celgene Corporation. PRE-/POST-INFUSION Select Important Safety Information MEDICATIONS *The first prescribed 16 mg/kg dose at Week 1 may be split over 2 consecutive days. See page 54 for details. WARNINGS AND PRECAUTIONS †For dosing instructions of combination agents administered with DARZALEX®, see Clinical Studies (14.1) section of the full Prescribing Infusion Reactions – DARZALEX® can cause severe and/or serious infusion reactions, Information for DARZALEX® and the respective manufacturer’s

prescribing information. including anaphylactic reactions. In clinical trials, approximately half of all patients ‡Please see the DARZALEX® full Prescribing Information for more experienced an infusion reaction. Most infusion reactions occurred during the first infusion

information regarding dexamethasone dosage and administration. and were Grade 1-2. Infusion reactions can also occur with subsequent infusions. CHECKLIST Please see Indications and full Important Safety Information on pages 46-49 and click here for 7 DARZALEX® full Prescribing Information. DR d management as needed. Permanently discontinue 1 Select Important Information therapy if an anaphylactic reaction or life-threatening

(Grade 4) reaction occurs and institute appropriate DVT d • DARZALEX ® should be administered by a emergency care. For patients with Grade 1, 2, or 3 healthcare professional with immediate reactions, reduce the infusion rate when re-starting the access to emergency equipment and infusion. appropriate medical support to manage DVMP infusion reactions if they occur To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients following • If a planned dose of DARZALEX® is missed, DARZALEX® infusions. Patients with a history of chronic administer the dose as soon as possible and obstructive pulmonary disease may require additional DV d adjust the dosing schedule accordingly, post-infusion medications to manage respiratory maintaining the treatment interval complications. Consider prescribing short- and long- acting bronchodilators and inhaled corticosteroids for Select Important Safety Information patients with chronic obstructive pulmonary disease. DP d CONTRAINDICATIONS Interference With Serological Testing – Daratumumab DARZALEX® (daratumumab) is contraindicated in binds to CD38 on red blood cells (RBCs) and results in patients with a history of severe hypersensitivity (eg, a positive Indirect Antiglobulin Test (Indirect Coombs MONOTHERAPY anaphylactic reactions) to daratumumab or any of test). Daratumumab-mediated positive indirect the components of the formulation. antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to WARNINGS AND PRECAUTIONS RBCs masks detection of antibodies to minor antigens Infusion Reactions – DARZALEX® can cause in the patient’s serum. The determination of a patient’s severe and/or serious infusion reactions, ABO and Rh blood type are not impacted. Notify blood IMPORTANT SAFETY

including anaphylactic reactions. In clinical trials, transfusion centers of this interference with serological INFORMATION approximately half of all patients experienced an testing and inform blood banks that a patient has infusion reaction. Most infusion reactions occurred received DARZALEX®. Type and screen patients prior to during the first infusion and were Grade 1-2. Infusion starting DARZALEX®. reactions can also occur with subsequent infusions. ® Neutropenia and Thrombocytopenia – DARZALEX may Nearly all reactions occurred during infusion or increase neutropenia and/or thrombocytopenia induced within 4 hours of completing DARZALEX®. Prior to the by background therapy. Monitor complete blood cell ADMINISTRATION introduction of post-infusion medication in clinical counts periodically during treatment according to the trials, infusion reactions occurred up to 48 hours manufacturer’s prescribing information for background after infusion. Severe reactions have occurred, therapies. Monitor patients with neutropenia for signs of including bronchospasm, hypoxia, dyspnea, infection. DARZALEX® dose delay may be required to hypertension, laryngeal edema, and pulmonary allow recovery of neutrophils and/or platelets. No dose edema. Signs and symptoms may include reduction of DARZALEX® is recommended. Consider INFUSION RATES respiratory symptoms, such as nasal congestion, & REACTIONS supportive care with growth factors for neutropenia or cough, throat irritation, as well as chills, vomiting, transfusions for thrombocytopenia. and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypotension.

Pre-medicate patients with antihistamines, PRE-/POST-INFUSION antipyretics, and corticosteroids. Frequently monitor MEDICATIONS patients during the entire infusion. Interrupt infusion for reactions of any severity and institute medical

Please see Indications and full Important Safety Information on pages 46-49 CHECKLIST and click here for DARZALEX® full Prescribing Information. 8 In adult patients with newly diagnosed, transplant-ineligible multiple myeloma Safety results demonstrated in combination with Rd Most frequent adverse reactions and laboratory abnormalities reported in ≥20% of patients and with at least a 5% greater frequency in the DARZALEX® + Rd arm1*

Adverse reactions DARZALEX® + Rd Rd Treatment-emergent event (%) (%) (%) (%) (%) (%) e e esto tt eto so etos ostto ee ee te ste Nse se o ots se sss eo ee seso eot e eese ette

*Adverse reactions that occurred with a frequency of ≥10% and <20%, and with at least a 5% greater frequency in the DARZALEX® + Rd arm were: headache, urinary tract infection, hyperglycemia, hypercalcemia, vomiting, chills, paresthesia, and hypertension. Serious adverse reactions (ARs) with at least a 2% greater incidence in the DRd arm compared to the Rd arm were pneumonia (DRd 15% vs Rd 8%), bronchitis (DRd 4% vs Rd 2%) and dehydration (DRd 2% vs Rd <1%).1

Laboratory abnormalities DARZALEX® + Rd Rd Treatment-emergent event (%) (%) (%) (%) (%) (%) Netoe eoe oe ootoe e

Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing Information. 9 DR d Safety results demonstrated in Notes:

combination with Rd in adult DVT d patients with newly diagnosed, transplant-ineligible multiple myeloma DVMP

• Discontinuation rates due to ARs: 7% with DRd vs 16% with Rd3

• Infusion reactions (IRs) with DRd occurred in 41% of DV d patients; 2% were Grade 3 and <1% were Grade 41 • IRs of any grade or severity may require

management by interruption, modification, DP d and/or discontinuation of the infusion1 • Most IRs occurred during the first infusion1 MONOTHERAPY See previous page for additional results. IMPORTANT SAFETY INFORMATION

ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing CHECKLIST

Information. 10 DR d DVT d DVMP DV d DP d MONOTHERAPY

DARZALEX® (daratumumab) + lenalidomide + IMPORTANT SAFETY

dexamethasone (DRd) INFORMATION DOSING & SAFETY

for adult patients with relapsed/refractory multiple myeloma ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

+ Rd dosing for patients with relapsed/ DVT d refractory multiple myeloma DARZALEX® dosing frequency decreases over time1

DVMP

oto t e eoe DV d eetsoe s oe

§The first prescribed 16 mg/kg dose at Week 1 may be split over 2 consecutive days. See page 54 for details. Recommended dosage DP d and schedule for DARZALEX®1

Doses given as 1 weekly infusion Per (Cycles 1* to 2; Weeks 1 to 8) MONOTHERAPY 4 Cycle

Doses given as 1 infusion every 2 weeks Per (twice per 4-week cycle; Cycles 3 to 6; 2 Cycle Weeks 9 to 24) Cycle 7 onward (each lasting 28 days)

Cycle 7 onward (each lasting 28 days) IMPORTANT SAFETY

given as 1 infusion every 4 weeks INFORMATION Dose Cycle 7 onward (each lasting 28 days) Per (Cycle 7+; Week 25+ until disease 1 Cycle progression) 23 estimated Year 1 infusion visits ADMINISTRATION See table on page 13 ▶ • Revlimid ® (lenalidomide) 25 mg is given orally on Days 1–21 of each cycle† • Dexamethasone 40 mg is given orally or IV once a week‡ — On DARZALEX® infusion days, 20 mg of the Infusion reactions of any grade or severity may be managed by interruption, modification, and/or discontinuation

® INFUSION RATES dexamethasone dose was given as a of the infusion. DARZALEX should be permanently discontinued upon the third occurrence of a Grade 3 infusion & REACTIONS pre-infusion medication and the remainder reaction and upon any occurrence of a Grade 4 infusion reaction. given the day after the infusion No dose reductions of DARZALEX® are recommended. Dose delay may be required to allow recovery of blood cell — For patients on a reduced dexamethasone counts in the event of hematological toxicity [see Warnings and Precautions (5.3, 5.4)]. For information concerning

dose, the entire 20-mg dose was given as a drugs given in combination with DARZALEX®, see manufacturer’s prescribing information. ®

DARZALEX pre-infusion medication PRE-/POST-INFUSION

Select Important Safety Information MEDICATIONS Revlimid® is a registered trademark of Celgene Corporation. *The first prescribed 16 mg/kg dose at Week 1 may be split over WARNINGS AND PRECAUTIONS 2 consecutive days. See page 54 for details. †For dosing instructions of combination agents administered with DARZALEX®, Infusion Reactions – DARZALEX® can cause severe and/or serious infusion reactions, see the Clinical Studies (14.2) section of the full Prescribing Information for including anaphylactic reactions. In clinical trials, approximately half of all patients DARZALEX® and the respective manufacturer’s prescribing information. ‡Please see the DARZALEX® full Prescribing Information for more information experienced an infusion reaction. Most infusion reactions occurred during the first regarding dexamethasone dosage and administration. infusion and were Grade 1-2. Infusion reactions can also occur with subsequent CHECKLIST Please see Indications and full Important Safety infusions. Information on pages 46-49 and click here for 13 DARZALEX® full Prescribing Information. DR d management as needed. Permanently discontinue 1 Select Important information therapy if an anaphylactic reaction or life-threatening

Please see Indications and full Important Safety Information on pages 46-49 CHECKLIST and click here for DARZALEX® full Prescribing Information. 14 In patients with relapsed/refractory multiple myeloma Safety results demonstrated in combination with Rd Most frequent adverse reactions and laboratory abnormalities reported in ≥20% of patients and with at least a 5% greater frequency in the DARZALEX® + Rd arm1*

Adverse reactions Treatment-emergent event e esto tt eto so etos e te o se sss Nse se e

*Adverse reactions that occurred with a frequency of ≥10% and <20%, and with at least a 5% greater frequency in the DARZALEX® + Rd arm were vomiting and headache. Serious adverse reactions (ARs) with at least a 2% greater incidence in the DRd arm compared with the Rd arm were pneumonia (DRd 12% vs Rd 10%), upper respiratory tract infection (DRd 7% vs Rd 4%), influenza, and pyrexia (DRd 3% vs Rd 1% for each).1

Laboratory abnormalities Treatment-emergent event e ootoe Netoe oe

Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing Information. 15 DR d Safety results demonstrated in Notes:

combination with Rd in patients with DVT d relapsed/refractory multiple myeloma

• Discontinuation rates due to ARs with DRd were DVMP similar to Rd alone (7% vs 8%, respectively)1 • Infusion reactions (IRs) with DRd occurred in 48% of patients; 5% were Grade 3 and 0% were Grade 41 DV d • Grade 3/4 infections between study arms: 27% vs 23% with DRd and Rd, respectively1

• IRs of any grade or severity may require DP d management by interruption, modification, and/or discontinuation of the infusion1

• Most IRs occurred during the first infusion MONOTHERAPY

See previous page for additional results. IMPORTANT SAFETY INFORMATION

ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing CHECKLIST

Information. 16 DR d DVT d DVMP DV d DP d MONOTHERAPY

DARZALEX® (daratumumab) + bortezomib + thalidomide + IMPORTANT SAFETY

dexamethasone (DVTd) INFORMATION DOSING & SAFETY

ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 and click here for CHECKLIST DARZALEX® full Prescribing Information. Induction Cycles 1−2 (each lasting 28 days) Total of 8 DARZALEX® doses

DARZALEX® (daratumumab) + VTd dosing DARZALEX® (daratumumab) + VTd dosing schedule for adult patients with newly 1 In adult patients with newly diagnosed multiple myeloma diagnosedoteoInduction Cycles multiple 1−2 (each myeloma lasting 28 days)who are eligible for autologousTotal of 8 DARZALEX stem ®cell doses transplant who are eligible for autologous stem cell transplant1 toe Induction Cycles 1−2 (each lasting 28 days) Total of 8 DARZALEX® doses eetsoeInduction Cycles 1−2 (each lasting 28 days) Total of 8 DARZALEX doses Dosing schedule based on a phase 3, randomized, active-controlled trial1 oto t ee oteo oteo o toe eetsoe Induction Cycles 3−4 (each lasting 28 days) Total of 4 DARZALEX® doses s oe oteotoe eetsoe Recommended dosage and toe schedule for DARZALEX®1 everyeetsoe 2 weeks § 1 Doses The first prescribed 16 mg/kg dose at Week 1 may be split over 2 consecutive days. See page 54 for details. given as 1 weekly infusion oteoInduction Cycles 3−4 (each lasting 28 days) Total of 4 DARZALEX® doses Per (Cycles 1* and 2; Weeks 1 to 8) Cycle toe ® 4 Induction Cycles 3−4 (each lasting 28 days) Total of 4 DARZALEX® doses eetsoeInduction Cycles 3−4 (each lasting 28 days) II II II II Total of 4 DARZALEX doses Doses Induction given as 1 infusion every 2 weeks (twice per Per every 2 weeks 2 Cycle 4–week cycle; Cycles 3 and 4; Weeks 9 to 16) everyoteoSTOP 2 FOR weeks HIGH DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM CELL TRANSPLANT STOP FOR HIGH DOSE CHEMOTHERAPY AND ASCT oteotoe II II II II given as 1 infusion every 2 weeks eetsoe DVT d Doses toe Per (twice per 4–week cycle; Cycles 5 and 6; II II II II eetsoe II II II II 2 Cycle Weeks 1 to 8 of consolidation phase) STOP FOR HIGH DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM CELL TRANSPLANT estimated total infusion visits Consolidation for induction and consolidation STOP FOR HIGH DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM CELL TRANSPLANT 16 ConsolidationSTOP FOR HIGH Cycles DOSE 5−6 (eachCHEMOTHERAPY lasting 28 days) AND AUTOLOGOUS STEMTotal ofCELL 4 DARZALEX TRANSPLANT® doses

See table on page 20 ▶ • Velcade ® (bortezomib) 1.3 mg/m2 BSA is given SC or IV on Days 1, 4, 8, and 11 of each cycle1† every 2 weeks ® • Thalomid (thalidomide) 100 mg is given orally oteo daily during each cycle1† Consolidation Cycles 5−6 (each lasting 28 days) Total of 4 DARZALEX® doses toe • Dexamethasone 40 mg is given orally or IV on Days 1, ® Consolidation Cycles 5−6 (eachII II lasting 28 days)II II II II Total of 4 DARZALEX doses 2, 8, 9, 15, 16, 22, and 23 of Cycles 1–2, and at 40 mg eetsoe on Days 1–2 and 20 mg on subsequent dosing days II20 mg dose. (Days 8, 9, 15, 16) of Cycles 3–4; dexamethasone 20 mg every 2 weeks is administered on Days 1, 2, 8, 9, 15, and 16 in Cycles 5–61‡ Infusion reactions of any grade or severity may be managed by interruption, modification, and/or discontinuation oteo ® — On DARZALEX® infusion days, dexamethasone is ofevery the infusion. 2 weeks DARZALEX should be permanently discontinued upon the third occurrence of a Grade 3 infusion 1 administered IV as a pre-infusion medication reactionoteotoe and upon any occurrence of a Grade 4 infusion reaction. Noeetsoe dose reductions of DARZALEXII ®II are recommended.II II Dose delay mayII II be required to allow recovery of blood cell ASCT=autologous stem cell transplant; BSA=body surface area; IV=intravenous; toe SC=subcutaneous. 1 counts in the event of hematologicalII II toxicity [seeII WarningsII and PrecautionsII II (5.3, 5.4)]. For information concerning ® eetsoe Thalomid is a registered trademark of Celgene Corporation. eetsoe ® Velcade ® is a registered trademark of Millennium Pharmaceuticals, Inc. drugs given in combination with DARZALEX , see manufacturer’s prescribing information. *The first prescribed 16 mg/kg dose at Week 1 may be split over 2 consecutive days.1 See page 54 for details. Select Important Safety Information †For dosing instructions of combination agents administered with DARZALEX®, see the Clinical Studies (14.1) section of the full Prescribing Information for DARZALEX® and the respective manufacturer’s prescribing information. CONTRAINDICATIONS ‡ ® Please see the DARZALEX full Prescribing Information for more information ® regarding dexamethasone dosage and administration. DARZALEX (daratumumab) is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation. Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing Information. 19 institute appropriate emergency care. For patients with 1 Select Important Information Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion. • DARZALEX ® should be administered by a healthcare professional with immediate To reduce the risk of delayed infusion reactions, access to emergency equipment and administer oral corticosteroids to all patients following appropriate medical support to manage DARZALEX® infusions. Patients with a history of chronic infusion reactions if they occur obstructive pulmonary disease may require additional post-infusion medications to manage respiratory • If a planned dose of DARZALEX® is missed, complications. Consider prescribing short- and long- administer the dose as soon as possible and acting bronchodilators and inhaled corticosteroids for adjust the dosing schedule accordingly, patients with chronic obstructive pulmonary disease. maintaining the treatment interval Interference With Serological Testing – Daratumumab binds to CD38 on red blood cells (RBCs) and results in Select Important Safety Information a positive Indirect Antiglobulin Test (Indirect Coombs CONTRAINDICATIONS test). Daratumumab-mediated positive indirect DARZALEX® (daratumumab) is contraindicated in antiglobulin test may persist for up to 6 months after the patients with a history of severe hypersensitivity (eg, last daratumumab infusion. Daratumumab bound to anaphylactic reactions) to daratumumab or any of RBCs masks detection of antibodies to minor antigens the components of the formulation. in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted. Notify blood WARNINGS AND PRECAUTIONS transfusion centers of this interference with serological Infusion Reactions – DARZALEX® can cause testing and inform blood banks that a patient has severe and/or serious infusion reactions, received DARZALEX®. Type and screen patients prior to including anaphylactic reactions. In clinical trials, starting DARZALEX®. approximately half of all patients experienced an Neutropenia and Thrombocytopenia – DARZALEX® may infusion reaction. Most infusion reactions occurred increase neutropenia and/or thrombocytopenia induced during the first infusion and were Grade 1-2. Infusion by background therapy. Monitor complete blood cell reactions can also occur with subsequent infusions. counts periodically during treatment according to the Nearly all reactions occurred during infusion or manufacturer’s prescribing information for background within 4 hours of completing DARZALEX®. Prior to the therapies. Monitor patients with neutropenia for signs of introduction of post-infusion medication in clinical infection. DARZALEX® dose delay may be required to trials, infusion reactions occurred up to 48 hours allow recovery of neutrophils and/or platelets. No dose after infusion. Severe reactions have occurred, reduction of DARZALEX® is recommended. Consider including bronchospasm, hypoxia, dyspnea, supportive care with growth factors for neutropenia or hypertension, laryngeal edema, and pulmonary transfusions for thrombocytopenia. edema. Signs and symptoms may include respiratory symptoms, such as nasal congestion, Interference With Determination of Complete Response – cough, throat irritation, as well as chills, vomiting, Daratumumab is a human IgG kappa monoclonal and nausea. Less common symptoms were antibody that can be detected on both the serum wheezing, allergic rhinitis, pyrexia, chest discomfort, protein electrophoresis (SPE) and immunofixation (IFE) pruritus, and hypotension. assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination Pre-medicate patients with antihistamines, of complete response and of disease progression in some antipyretics, and corticosteroids. Frequently monitor patients with IgG kappa myeloma protein. patients during the entire infusion. Interrupt infusion for reactions of any severity and institute medical management as needed. Permanently discontinue Please see Indications therapy if an anaphylactic reaction or life- and full Important Safety Information on pages threatening (Grade 4) reaction occurs and 46-49 and click here for DARZALEX® full Prescribing Information. 20 Safety results demonstrated in combination with VTd Most frequent adverse reactions and laboratory abnormalities reported in ≥20% of patients and with at least a 5% greater frequency in the DARZALEX® (daratumumab) + VTd arm1*

Adverse reactions DARZALEX® + VTd VTd Treatment-emergent event (%) Adverse(%) reactions (%) (%) (%) (%) so etos DARZALEX® + VTd VTd NseTreatment-emergent event (%) (%) (%) (%) (%) (%) soe esto etos tt eto Nsee eots esto tt eto e *Adverse reactions that occurred with a frequency of ≥10% and <20%, and with at least a 5% greater frequency in the ots DARZALEX® + VTd arm were: cough, vomiting, and hypertension. Serious adverse reactions with a 2% greater incidence in the DVTd arm compared with the VTd arm were bronchitis (DVTd 2% vs VTd <1%) and pneumoniaLaboratory (DVTd abnormalities 6% vs VTd 4%).1 DARZALEX® + VTd VTd Treatment-emergent event (%) Laboratory(%) abnormalities(%) (%) (%) (%) oe DARZALEX® + VTd VTd eoeTreatment-emergent event (%) (%) (%) (%) (%) (%) oeootoe eoeNetoe ootoee Netoe e

Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing Information. 21 Safety results demonstrated Post-infusion medications are in combination with VTd recommended • Discontinuation rates due to any adverse event: 1 7% with DVTd vs 8% with VTd2 Post-infusion medications • Infusion reactions (IRs) with DVTd occurred To reduce the risk of delayed infusion reactions, in 35% of patients; 3% were Grade 3 and administer the day after every infusion as follows: <1% were Grade 41 • Most IRs occurred during the first infusion1 Oral corticosteroid (≤20 mg methylprednisolone — 27% of patients had IRs with the first infusion2 or equivalent); however, if a background — 11% of patients had IRs with the first regimen-specific corticosteroid (eg, post-transplant infusion1 dexamethasone, prednisone) is administered the day after the DARZALEX® infusion, • Grade 3/4 infections were similar between additional post-infusion medications may not study arms: 22% vs 20% with DVTd vs VTd be needed alone, respectively1 During monotherapy, administer oral See previous page for additional results. corticosteroid (20 mg methylprednisolone or equivalent dose of an intermediate-acting Important information or long-acting corticosteroid in accordance before administering with local standards) on each of the 2 days DARZALEX® (daratumumab) following all DARZALEX® infusions (beginning the day after the infusion) Pre-infusion medications1 Note: For patients with a history of chronic obstructive pulmonary disorder, consider including short- and long- acting bronchodilators and inhaled corticosteroids. To reduce the risk of infusion reactions, administer Following the first 4 infusions, if the patient experiences no to all patients approximately 1 to 3 hours prior to major infusion reactions, these additional inhaled post- every infusion as follows: infusion medications may be discontinued. Dexamethasone 20 mg prior to every DARZALEX® infusion. When dexamethasone is the background regimen-specific More dosing and administration corticosteroid, the dexamethasone treatment information for DARZALEX® dose will also serve as premedication on DARZALEX® infusion days* For information on preparation for administration, During monotherapy, methylprednisolone infusion rates, management of infusion reactions, ® 100 mg, or equivalent, administered and how DARZALEX is supplied, please see the intravenously. Following the second infusion, accompanying guide, Dosing & Administration ® the dose of corticosteroid may be reduced for DARZALEX (daratumumab), and the full (oral or intravenous methylprednisolone 60 mg) Prescribing Information. Oral antipyretics (acetaminophen 650 to 1000 mg), plus Oral or IV antihistamine (diphenhydramine 25 to 50 mg or equivalent) *Dexamethasone is given intravenously prior to the first DARZALEX® infusion and oral administration may be Please see Indications considered prior to subsequent infusions. Additional and full Important background regimen-specific corticosteroids (eg, prednisone) should not be taken on DARZALEX® Safety Information on infusion days when patients receive dexamethasone pages 46-49 and click (or equivalent) as pre-medication. here for DARZALEX® full Prescribing Information. 22 DR d DVT d DVMP DV d DP d MONOTHERAPY

DARZALEX® (daratumumab) + IMPORTANT SAFETY

bortezomib + melphalan + INFORMATION prednisone (DVMP)

DOSING & SAFETY ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

+ VMP dosing DVT d In adult patients with newly diagnosed, DARZALEX® dosing frequency decreases over time1 transplant-ineligible multiple myeloma

C T DARAE d DVMP Dosing schedule based on a phase 3, randomized, active-controlled trial4 Day 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 DARAE

oto t ee oteo bortezomib DV d

e esoe s melphalan/prednisone oe *The first prescribed 16 mg/kg dose at Week 1 may be split over 2 consecutive days. See page 54 for details.

Recommended dosage C - T DARAE d DP d ®1 and schedule for DARZALEX Day 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 DARAE Doses given as 1 weekly infusion bortezomib MONOTHERAPY Per (Cycle 1*; Weeks 1 to 6) 6 Cycle melphalan/prednisone Doses given as 1 infusion every 3 weeks C DARAE d dd Per (twice per 6-week cycle; Cycles 2 to 9; C 2 Cycle Weeks 7 to 54) Day 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 DARAE IMPORTANT SAFETY Dose given as 1 infusion every 4 weeks INFORMATION Per (Cycles 10+; Weeks 55+ until 1 Cycle disease progression) Infusion reactions of any grade or severity may be managed by interruption, modification, and/or discontinuation of the infusion. DARZALEX® should be permanently discontinued upon the third occurrence of a Grade 3 infusion reaction and upon any occurrence of a Grade 4 infusion reaction. estimated Year 1 infusion visits 22 No dose reductions of DARZALEX® are recommended. Dose delay may be required to allow recovery of blood cell counts in the event of hematological toxicity [see Warnings and Precautions (5.3, 5.4)]. For information concerning ADMINISTRATION See table on page 26 ▶ drugs given in combination with DARZALEX®, see manufacturer’s prescribing information. • Velcade ® (bortezomib) was administered by subcutaneous (SC) injection at a dose of 1.3 mg/m2 twice weekly at Weeks 1, 2, 4, and 5 for the first 6-week cycle (Cycle 1; 8 doses), followed by once weekly administrations at Weeks 1, 2, 4, INFUSION RATES and 5 for eight more 6-week cycles (Cycles 2–9; & REACTIONS 4 doses per cycle) • Melphalan at 9 mg/m2 and prednisone at 2 60 mg/m were orally administered on Days 1 to 4 of the nine 6-week cycles (Cycles 1–9) Select Important Safety Information PRE-/POST-INFUSION ®

• DARZALEX treatment was continued until MEDICATIONS disease progression or unacceptable toxicity WARNINGS AND PRECAUTIONS ® *The first prescribed 16 mg/kg dose at Week 1 may be split over Infusion Reactions – DARZALEX can cause severe and/or serious infusion reactions, 2 consecutive days. See page 54 for details. including anaphylactic reactions. In clinical trials, approximately half of all patients Velcade ® is a registered trademark of Millennium Pharmaceuticals, Inc. experienced an infusion reaction. Most infusion reactions occurred during the first For dosing instructions of combination agents administered with DARZALEX®, infusion and were Grade 1-2. Infusion reactions can also occur with subsequent see the Clinical Studies (14.1) section of the full Prescribing Information for ® infusions.

DARZALEX and the respective manufacturer’s prescribing information. CHECKLIST Please see Indications and full Important Safety Information on pages 46-49 and click here for 25 DARZALEX® full Prescribing Information. DR d management as needed. Permanently discontinue Select Important Information1 therapy if an anaphylactic reaction or life-threatening

Please see Indications and full Important Safety Information on pages 46-49 CHECKLIST and click here for DARZALEX® full Prescribing Information. 26 Safety results demonstrated in combination with VMP Most frequent adverse reactions and laboratory abnormalities reported in ≥10% of patients and with at least a 5% greater frequency in the DARZALEX® + VMP arm1

Adverse reactions DARZALEX® + VMP VMP Treatment-emergent event e esto tt eto so etos e ee eo o se eteso

Serious adverse reactions with at least a 2% greater incidence in the DVMP arm compared to the VMP arm were pneumonia (DVMP 11% vs VMP 4%), upper respiratory tract infection (DVMP 5% vs VMP 1%), and pulmonary edema (DVMP 2% vs VMP 0%).1

Laboratory abnormalities DARZALEX® + VMP VMP Treatment-emergent event e ootoe Netoe oe

• Discontinuation rates due to any adverse event: 4.9% with DVMP vs 9.3% with VMP alone4 • Infusion reactions (IRs) with DARZALEX® + VMP occurred in 28% of patients; 4% were Grade 3 and 1% were Grade 41

Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing Information. 27 DR d Safety results demonstrated in Notes:

combination with VMP DVT d

• Grade 3 or 4 infections were 23% with DVMP vs 15% with VMP alone1 DVMP • IRs of any grade or severity may require management by interruption, modification, 1 and/or discontinuation of the infusion DV d • Most IRs occurred during the first infusion1

See previous page for additional results. DP d MONOTHERAPY IMPORTANT SAFETY INFORMATION

ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing CHECKLIST

Information. 28 DR d DVT d DVMP DV d DP d MONOTHERAPY

DARZALEX® (daratumumab) + bortezomib + IMPORTANT SAFETY

dexamethasone (DVd) INFORMATION DOSING & SAFETY

ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

DARZALEX® dosing frequency decreases over time1 DVT d DVMP

oto t ee oteo eetsoe s oe DV d

Recommended dosage and schedule for DARZALEX®1 DP d

§ Doses given as 1 weekly infusion The first prescribed 16 mg/kg dose at Week 1 may be split over 2 consecutive days. See page 54 for details. Per (Cycles 1* to 3; Weeks 1 to 9) 3 Cycle MONOTHERAPY Dose given as 1 infusion every 3 weeks Per (once per 3-week cycle; Cycles 4 to 8; 1 Cycle Weeks 10 to 24)

Dose given as 1 infusion every 4 weeks Per (Cycles 9+; Weeks 25+ until disease IMPORTANT SAFETY

1 Cycle progression) INFORMATION

estimated Year 1 infusion visits 21 Cycle 9 onward (each lasting 28 days)

See table on page 32 ▶ ® • Velcade (bortezomib) is administered by 2 subcutaneous injection or IV infusion on Days 1, 4, ADMINISTRATION 8, and 11 of each cycle for a total of 8 cycles† • Dexamethasone 20 mg is given orally once Note: Bortezomib and dexamethasone dosing should be stopped after 8 cycles. daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 for a Infusion reactions of any grade or severity may be managed by interruption, modification, and/or discontinuation total of 8 cycles‡ of the infusion. DARZALEX® should be permanently discontinued upon the third occurrence of a Grade 3 infusion — On the days of DARZALEX® infusion, 20 mg reaction and upon any occurrence of a Grade 4 infusion reaction. INFUSION RATES of the dexamethasone dose was No dose reductions of DARZALEX® are recommended. Dose delay may be required to allow recovery of blood cell & REACTIONS administered as a pre-infusion medication and counts in the event of hematological toxicity [see Warnings and Precautions (5.3, 5.4)]. For information concerning was continued as a pre-medication drugs given in combination with DARZALEX®, see manufacturer’s prescribing information. after Vd discontinuation

— For patients on a reduced dexamethasone Select Important Safety Information

dose, the entire 20-mg dose was given as PRE-/POST-INFUSION

a DARZALEX® pre-infusion medication MEDICATIONS WARNINGS AND PRECAUTIONS Velcade ® is a registered trademark of Millennium Pharmaceuticals, Inc. Infusion Reactions – DARZALEX® can cause severe and/or serious infusion reactions, *The first prescribed 16 mg/kg dose at Week 1 may be split over 2 consecutive days. See page 54 for details. including anaphylactic reactions. In clinical trials, approximately half of all patients †Please refer to the bortezomib prescribing information for more detailed experienced an infusion reaction. Most infusion reactions occurred during the first information about twice-weekly bortezomib dosing. infusion and were Grade 1-2. Infusion reactions can also occur with subsequent ‡Please see the DARZALEX® full Prescribing Information for more information infusions.

regarding dexamethasone dosage and administration. CHECKLIST Please see Indications and full Important Safety Information on pages 46-49 and click here for 31 DARZALEX® full Prescribing Information. DR d

1 management as needed. Permanently discontinue Select Important Information therapy if an anaphylactic reaction or life-threatening

(Grade 4) reaction occurs and institute appropriate DVT d • DARZALEX® should be administered by a emergency care. For patients with Grade 1, 2, or 3 healthcare professional with immediate reactions, reduce the infusion rate when re-starting the access to emergency equipment and infusion. appropriate medical support to manage DVMP infusion reactions if they occur To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients following • If a planned dose of DARZALEX® is missed, DARZALEX® infusions. Patients with a history of chronic administer the dose as soon as possible and obstructive pulmonary disease may require additional DV d adjust the dosing schedule accordingly, post-infusion medications to manage respiratory maintaining the treatment interval complications. Consider prescribing short- and long- acting bronchodilators and inhaled corticosteroids for Select Important Safety Information patients with chronic obstructive pulmonary disease. DP d CONTRAINDICATIONS Interference With Serological Testing – Daratumumab DARZALEX® (daratumumab) is contraindicated in binds to CD38 on red blood cells (RBCs) and results in patients with a history of severe hypersensitivity (eg, a positive Indirect Antiglobulin Test (Indirect Coombs MONOTHERAPY anaphylactic reactions) to daratumumab or any of test). Daratumumab-mediated positive indirect the components of the formulation. antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to WARNINGS AND PRECAUTIONS RBCs masks detection of antibodies to minor antigens Infusion Reactions – DARZALEX® can cause in the patient’s serum. The determination of a patient’s severe and/or serious infusion reactions, ABO and Rh blood type are not impacted. Notify blood IMPORTANT SAFETY

Please see Indications and full Important Safety Information on pages 46-49 CHECKLIST and click here for DARZALEX® full Prescribing Information. 32 Safety results demonstrated in combination with Vd Most frequent adverse reactions and laboratory abnormalities reported in ≥20% of patients and with at least a 5% greater frequency in the DARZALEX® + Vd arm1*

Adverse reactions

Treatment-emergent event

ee seso eot so etos e esto tt eto

e o e ee se

*Adverse reactions that occurred with a frequency of ≥10% and <20%, and with at least a 5% greater frequency in the DARZALEX® + Vd arm were pyrexia and vomiting. Serious adverse reactions (ARs) with at least a 2% greater incidence in the DVd arm compared with the Vd arm were upper respiratory tract infection (DVd 5% vs Vd 2%), diarrhea, and atrial fibrillation (DVd 2% vs Vd 0% for each).1

Laboratory abnormalities

Treatment-emergent event e ootoe Netoe oe

• Discontinuation rates due to ARs with DVd were similar to Vd alone (7% vs 9%, respectively)1

Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing Information. 33 DR d Safety results demonstrated in Notes:

combination with Vd DVT d

• Infusion reactions (IRs) with DVd occurred in 45% DVMP of patients; 9% were Grade 3 and 0% were Grade 41 • Grade 3/4 infections were similar between study arms: 21% vs 19% with DVd vs Vd alone, respectively1 DV d • IRs of any grade or severity may require management by interruption, modification, and/or 1

discontinuation of the infusion DP d • Most IRs occurred during the first infusion1

See previous page for additional results. MONOTHERAPY IMPORTANT SAFETY INFORMATION

ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing CHECKLIST

Information. 34 DR d DVT d DVMP DV d DP d MONOTHERAPY

DARZALEX® (daratumumab) + pomalidomide + IMPORTANT SAFETY

dexamethasone (DPd) INFORMATION DOSING & SAFETY

ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 and click here for CHECKLIST DARZALEX® full Prescribing Information. DR d DARZALEX® (daratumumab) + Pd dosing DARZALEX® + Pd dosing schedule Cycles 12 (each lasting 28 days) Total of 8 DARZALEX® doses ® 1 DVT d DARZALEX dosing frequency decreases over time ® In patients with ≥2 prior lines of therapy including Cycles 12 (each lasting 28 days) Total of 8 DARZALEX doses lenalidomide and a proteasome inhibitor (PI)1 ® DARZALEXCycles 12 (each® lasting 28 days) Total of 8 DARZALEX ® doses ® DARZALEXweekly DVMP Dosing schedule based on a phase 1b, Rest weekly ® 1,5 DARZALEXooe® open-label trial DARZALEX Rest eetsoeooeweekly Rest

ooeeetsoe Rest DV d oto t ost ooe ooe eetsoe N eetsoe Cycles 36 (each lasting 28 days) Total of 8 DARZALEX® doses § The first prescribed 16 mg/kg dose at Week 1 may be split over 2 consecutive days. See page 54 for details. ® Cycles 36 (each lasting 28 days) Total of 8 DARZALEX doses DP d Recommended dosage ® ® DARZALEXCycles 36 (each lasting 28 days) Total of 8 DARZALEX ® doses ®1 Cycles 36 (each lasting 28 days) Total of 8 DARZALEX doses and schedule for DARZALEX ® every 2 weeks DARZALEX Doses ® Rest given as 1 weekly infusion ooeevery 2 weeks®

DARZALEX MONOTHERAPY Per (Cycles 1* to 2; Weeks 1 to 8) DARZALEX Rest Cycle eetsoeooeevery 2 weeks 4 Rest ooeeetsoe Rest Doses given as 1 infusion every 2 weeks eetsoe Per (twice per 4-week cycle; Cycles 3 to 6; Cycle 7 onward (each lasting 28 days) 2 Cycle Weeks 9 to 24) Cycle 7 onward (each lasting 28 days) ® IMPORTANT SAFETY Dose given as 1 infusion every 4 weeks DARZALEXCycle 7 onward (each lasting 28 days) INFORMATION ® Per (Cycle 7+; Week 25+ until disease DARZALEXevery 4 weeks 1 Cycle progression) ® Rest DARZALEXooeevery 4 weeks® DARZALEX Rest eetsoeooeevery 4 weeks estimated Year 1 infusion visits Rest 23 ooeeetsoe Rest See table on page 38 ▶ eetsoe ADMINISTRATION • Pomalyst® (pomalidomide) 4 mg is given orally on Days 1–21 of each cycle† ® • Dexamethasone 40 mg is given orally or Continue DARZALEX + Pd until disease progression or unacceptable toxicity IV once a week‡ Continue DARZALEX® + Pd until disease progression or unacceptable toxicity ® Infusion reactions of any grade® or severity may be managed by interruption, modification, and/or discontinuation — On DARZALEX infusion days, 20 mg of the ® Continue DARZALEX® + Pd until disease progression or unacceptable toxicity of the infusion. DARZALEX should be permanently discontinued upon the third occurrence of a Grade 3 infusion INFUSION RATES

dexamethasone dose was given as a & REACTIONS pre-infusion medication and the remainder reaction and upon any occurrence of a Grade 4 infusion reaction. given the day after the infusion No dose reductions of DARZALEX® are recommended. Dose delay may be required to allow recovery of blood cell — For patients on a reduced dexamethasone counts in the event of hematological toxicity [see Warnings and Precautions (5.3, 5.4)]. For information concerning dose, the entire 20-mg dose was given as a drugs given in combination with DARZALEX®, see manufacturer’s prescribing information. DARZALEX® pre-infusion medication Select Important Safety Information PRE-/POST-INFUSION MEDICATIONS Pomalyst® is a registered trademark of Celgene Corporation. *The first prescribed 16 mg/kg dose at Week 1 may be split over WARNINGS AND PRECAUTIONS 2 consecutive days. See page 54 for details. ® †Please refer to the pomalidomide prescribing information for more Infusion Reactions – DARZALEX can cause severe and/or serious infusion reactions, detailed information about pomalidomide dosing. including anaphylactic reactions. In clinical trials, approximately half of all patients ‡Please see the DARZALEX® full Prescribing Information for more experienced an infusion reaction. Most infusion reactions occurred during the first information regarding dexamethasone dosage and administration. infusion and were Grade 1-2. Infusion reactions can also occur with subsequent CHECKLIST Please see Indications and full Important Safety infusions. Information on pages 46-49 and click here for 37 DARZALEX® full Prescribing Information. DR d management as needed. Permanently discontinue 1 Select Important Information therapy if an anaphylactic reaction or life-threatening

Please see Indications and full Important Safety Information on pages 46-49 CHECKLIST and click here for DARZALEX® full Prescribing Information. 38 Safety results demonstrated in combination with Pd

Most frequent adverse reactions and laboratory abnormalities reported in ≥20% of patients1*

Adverse reactions Laboratory abnormalities DARZALEX® + Pd DARZALEX® + Pd (N=103) N Treatment-emergent Any grade Grade 3 Grade 4 Treatment-emergent Any grade Grade 3 Grade 4 event (%) (%) (%) event (%) (%) (%) Fatigue 50 10 0 e

Upper respiratory ootoe 50 4 1 tract infection Netoe Infusion reactions 50 4 0 oe Cough 43 1 0

Diarrhea 38 3 0

Dyspnea 33 6 1

Constipation 33 0 0

Nausea 30 0 0

Muscle spasms 26 1 0

Back pain 25 6 0

Pyrexia 25 1 0

Insomnia 23 2 0

Arthralgia 22 2 0

Vomiting 21 2 0

Dizziness 21 2 0

Chills 20 0 0

*Adverse reactions that occurred with a frequency of ≥10% and <20% were: tremor, headache, edema peripheral, hypokalemia, nasal congestion, asthenia, noncardiac chest pain, pneumonia, pain in extremity, bone pain, hyperglycemia, musculoskeletal chest pain, anxiety, pain, and decreased appetite. The overall incidence of serious adverse reactions (ARs) was 49%. Serious ARs reported in ≥5% of patients included pneumonia (7%).1 Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing Information. 39 DR d Safety results demonstrated in Notes:

combination with Pd DVT d

• Discontinuation rate due to ARs with DPd was 13%1 DVMP • Infusion reactions (IRs) with DPd occurred in 50% of patients; 4% were Grade 3 and 0% were Grade 41

• Grade 3/4 infections were reported in 28% of DV d patients treated with DPd1 • IRs of any grade or severity may require

ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing CHECKLIST

Information. 40 DR d DVT d DVMP DV d DP d MONOTHERAPY

DARZALEX® (daratumumab) MONOTHERAPY IMPORTANT SAFETY

(single agent) INFORMATION DOSING & SAFETY

ADMINISTRATION INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

agent1,6

† DV d †The first prescribed 16 mg/kg dose at Week 1 may be split over 2 consecutive days. See page 54 for details. DP d Recommended dosage and schedule for DARZALEX®1 MONOTHERAPY Doses given as 1 weekly infusion Per (Cycles 1* to 2; Weeks 1 to 8) 4 Cycle

Doses given as 1 infusion every 2 weeks Cycle 7 onward (each lasting 28 days) Per (twice per 4-week cycle; Cycles 3 to 6;

2 Cycle Weeks 9 to 24) IMPORTANT SAFETY INFORMATION

Dose given as 1 infusion every 4 weeks Per (Cycle 7+; Week 25+ until disease

1 Cycle progression) ADMINISTRATION 23 estimated Year 1 infusion visits See table on page 44 ▶ Infusion reactions of any grade or severity may be managed by interruption, modification, and/or discontinuation ® • Administer DARZALEX only as an IV infusion of the infusion. DARZALEX® should be permanently discontinued upon the third occurrence of a Grade 3 infusion after dilution reaction and upon any occurrence of a Grade 4 infusion reaction. INFUSION RATES & REACTIONS • To reduce the risk of delayed infusion reactions, No dose reductions of DARZALEX® are recommended. Dose delay may be required to allow recovery of blood cell administer the day after every infusion as follows: counts in the event of hematological toxicity [see Warnings and Precautions (5.3, 5.4)]. During monotherapy, administer oral corticosteroid

(20 mg methylprednisolone or equivalent dose of an intermediate-acting or long-acting corticosteroid Select Important Safety Information in accordance with local standards) on each of PRE-/POST-INFUSION MEDICATIONS the 2 days following all DARZALEX® infusions. WARNINGS AND PRECAUTIONS

Note: For patients with a history of chronic obstructive pulmonary ® disorder, consider including short- and long-acting bronchodilators Infusion Reactions – DARZALEX can cause severe and/or serious infusion reactions, and inhaled corticosteroids. Following the first 4 infusions, if the including anaphylactic reactions. In clinical trials, approximately half of all patients patient experiences no major infusion reactions, these additional inhaled post-infusion medications may be discontinued. experienced an infusion reaction. Most infusion reactions occurred during the first infusion and were Grade 1-2. Infusion reactions can also occur with subsequent *The first prescribed 16 mg/kg dose at Week 1 may be split over 2 consecutive days. See page 54 for details. infusions. CHECKLIST Please see Indications and full Important Safety Information on pages 46-49 and click here for 43 DARZALEX® full Prescribing Information. DR d ® Select Important Information1 Safety results with DARZALEX Safety results (cont’d)

monotherapy DVT d • DARZALEX ® should be administered by a healthcare professional with immediate Most frequent adverse reactions and • Discontinuation rate due to any adverse event: 4%1 access to emergency equipment and laboratory abnormalities reported in ≥20% • Infusion reactions (IRs) with DARZALEX® occurred in 48% appropriate medical support to manage 1 DVMP of patients * of patients; 3% were Grade 3 and 0% were Grade 41 infusion reactions if they occur • IRs of any grade or severity may require management • If a planned dose of DARZALEX® is missed, Adverse reactions by interruption, modification, and/or discontinuation of administer the dose as soon as possible and DARZALEX® N Treatment-emergent the infusion1 DV d adjust the dosing schedule accordingly, event • Most IRs occurred during the first infusion1 maintaining the treatment interval so etos te Select Important Safety Information DP d Nse CONTRAINDICATIONS Select Important Safety Information DARZALEX® (daratumumab) is contraindicated in o Neutropenia and Thrombocytopenia – DARZALEX® patients with a history of severe hypersensitivity (eg, MONOTHERAPY may increase neutropenia and/or thrombocytopenia anaphylactic reactions) to daratumumab or any of e induced by background therapy. Monitor complete the components of the formulation. e esto blood cell counts periodically during treatment tt eto WARNINGS AND PRECAUTIONS according to the manufacturer’s prescribing information Infusion Reactions – DARZALEX® can cause *Adverse reactions that occurred with a frequency of ≥10% and for background therapies. Monitor patients with ® severe and/or serious infusion reactions, <20% were: arthralgia, nasal congestion, diarrhea, decreased neutropenia for signs of infection. DARZALEX dose appetite, nasopharyngitis, constipation, pain in extremity, delay may be required to allow recovery of neutrophils IMPORTANT SAFETY

including anaphylactic reactions. In clinical trials, INFORMATION ® approximately half of all patients experienced an dyspnea, vomiting, headache, musculoskeletal chest pain, and/or platelets. No dose reduction of DARZALEX pneumonia, chills, and hypertension. infusion reaction. Most infusion reactions occurred is recommended. Consider supportive care with during the first infusion and were Grade 1-2. Infusion Serious adverse reactions were reported in 33% of growth factors for neutropenia or transfusions for reactions can also occur with subsequent infusions. patients. The most frequent serious adverse reactions thrombocytopenia.

Nearly all reactions occurred during infusion or were pneumonia (6%), general physical health within 4 hours of completing DARZALEX®. Prior to the deterioration (3%), and pyrexia (3%).1 ADMINISTRATION introduction of post-infusion medication in clinical trials, infusion reactions occurred up to 48 hours Laboratory abnormalities after infusion. Severe reactions have occurred, DARZALEX® N including bronchospasm, hypoxia, dyspnea, Treatment-emergent hypertension, laryngeal edema, and pulmonary event edema. Signs and symptoms may include INFUSION RATES respiratory symptoms, such as nasal congestion, & REACTIONS cough, throat irritation, as well as chills, vomiting, and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypotension. PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 CHECKLIST and click here for DARZALEX® 44 full Prescribing Information. 45 DR d Indications and Important Safety

Information DVT d Indications Permanently discontinue therapy if an anaphylactic DARZALEX® is a CD38-directed cytolytic antibody reaction or life-threatening (Grade 4) reaction occurs indicated for the treatment of adult patients with and institute appropriate emergency care. For patients multiple myeloma: with Grade 1, 2, or 3 reactions, reduce the infusion rate DVMP when re-starting the infusion. • in combination with lenalidomide and dexamethasone in newly diagnosed patients who are To reduce the risk of delayed infusion reactions, ineligible for autologous stem cell transplant and in administer oral corticosteroids to all patients following ®

patients with relapsed or refractory multiple myeloma DARZALEX infusions. Patients with a history of chronic DV d who have received at least one prior therapy obstructive pulmonary disease may require additional • in combination with bortezomib, melphalan and post-infusion medications to manage respiratory prednisone in newly diagnosed patients who are complications. Consider prescribing short- and long- ineligible for autologous stem cell transplant acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease. DP d • in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are Interference With Serological Testing – Daratumumab eligible for autologous stem cell transplant binds to CD38 on red blood cells (RBCs) and results in • in combination with bortezomib and dexamethasone in a positive Indirect Antiglobulin Test (Indirect Coombs patients who have received at least one prior therapy test). Daratumumab-mediated positive indirect MONOTHERAPY antiglobulin test may persist for up to 6 months after the • in combination with pomalidomide and last daratumumab infusion. Daratumumab bound to dexamethasone in patients who have received at RBCs masks detection of antibodies to minor antigens least two prior therapies including lenalidomide and a in the patient’s serum. The determination of a patient’s proteasome inhibitor ABO and Rh blood type are not impacted. Notify blood • as monotherapy, in patients who have received at transfusion centers of this interference with serological least three prior lines of therapy including a testing and inform blood banks that a patient has ® proteasome inhibitor (PI) and an immunomodulatory received DARZALEX . Type and screen patients prior to IMPORTANT SAFETY agent or who are double-refractory to a PI and an starting DARZALEX®. INFORMATION immunomodulatory agent Neutropenia and Thrombocytopenia – DARZALEX® may Important Safety Information increase neutropenia and/or thrombocytopenia induced by background therapy. Monitor complete blood cell CONTRAINDICATIONS counts periodically during treatment according to the DARZALEX® (daratumumab) is contraindicated in manufacturer’s prescribing information for background patients with a history of severe hypersensitivity (eg, therapies. Monitor patients with neutropenia for signs of anaphylactic reactions) to daratumumab or any of the infection. DARZALEX® dose delay may be required to ADMINISTRATION components of the formulation. allow recovery of neutrophils and/or platelets. No dose reduction of DARZALEX® is recommended. Consider WARNINGS AND PRECAUTIONS supportive care with growth factors for neutropenia or Infusion Reactions – DARZALEX® can cause severe transfusions for thrombocytopenia. and/or serious infusion reactions, including anaphylactic reactions. In clinical trials, approximately half of all Interference With Determination of Complete Response – patients experienced an infusion reaction. Most Daratumumab is a human IgG kappa monoclonal

antibody that can be detected on both the serum INFUSION RATES infusion reactions occurred during the first infusion & REACTIONS and were Grade 1-2. Infusion reactions can also protein electrophoresis (SPE) and immunofixation (IFE) occur with subsequent infusions. Nearly all reactions assays used for the clinical monitoring of endogenous occurred during infusion or within 4 hours of completing M-protein. This interference can impact the determination DARZALEX®. Prior to the introduction of post-infusion of complete response and of disease progression in some medication in clinical trials, infusion reactions occurred patients with IgG kappa myeloma protein. up to 48 hours after infusion. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, PRE-/POST-INFUSION hypertension, laryngeal edema, and pulmonary edema. MEDICATIONS Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypotension. Pre-medicate patients with antihistamines, antipyretics, Please click here for and corticosteroids. Frequently monitor patients during DARZALEX® full Prescribing CHECKLIST the entire infusion. Interrupt infusion for reactions of any Information. severity and institute medical management as needed. 47 DR d Indications and Important Safety

Information (cont’d) DVT d Adverse Reactions – The most frequently reported adverse DARZALEX® in combination with bortezomib, reactions (incidence ≥20%) were: infusion reactions, thalidomide, and dexamethasone (DVTd): The most neutropenia, thrombocytopenia, fatigue, asthenia, frequent adverse reactions (≥20%) were infusion nausea, diarrhea, constipation, decreased appetite, reactions (35%), nausea (30%), upper respiratory tract DVMP vomiting, muscle spasms, arthralgia, back pain, pyrexia, infection (27%), pyrexia (26%), and bronchitis (20%). chills, dizziness, insomnia, cough, dyspnea, peripheral Serious adverse reactions (≥2% compared to the edema, peripheral sensory neuropathy, bronchitis, VTd arm) were bronchitis (DVTd 2% vs VTd <1%) and

pneumonia and upper respiratory tract infection. pneumonia (DVTd 6% vs VTd 4%). Treatment-emergent DV d DARZALEX® in combination with lenalidomide and Grade 3-4 hematology laboratory abnormalities (≥20%) dexamethasone (DRd): The most frequent (≥20%) adverse were lymphopenia (59%), neutropenia (33%), and reactions for newly diagnosed or relapsed refractory leukopenia (24%). ®

patients were, respectively, infusion reactions (41%, 48%), DARZALEX in combination with pomalidomide and DP d diarrhea (57%, 43%), nausea (32%, 24%), fatigue (40%, dexamethasone (DPd): The most frequent adverse 35%), pyrexia (23%, 20%), upper respiratory tract infection reactions (>20%) were fatigue (50%), infusion reactions (52%, 65%), muscle spasms (29%, 26%), dyspnea (32%, (50%), upper respiratory tract infection (50%), cough 21%), and cough (30%, 30%). In newly diagnosed patients, (43%), diarrhea (38%), constipation (33%), dyspnea constipation (41%), peripheral edema (41%), back pain (33%), nausea (30%), muscle spasms (26%), back MONOTHERAPY (34%), asthenia (32%), bronchitis (29%), pneumonia pain (25%), pyrexia (25%), insomnia (23%), arthralgia (26%), decreased appetite (22%), and peripheral sensory (22%), dizziness (21%), and vomiting (21%). The overall neuropathy (24%) were also reported. In newly diagnosed incidence of serious adverse reactions was 49%. Serious patients, serious adverse reactions (≥2% compared to Rd) adverse reactions reported in ≥5% of patients included were dehydration (2%), bronchitis (4%), and pneumonia pneumonia (7%). Treatment-emergent Grade 3-4 (15%), and treatment-emergent Grade 3-4 hematology hematology laboratory abnormalities (≥20%) were laboratory abnormalities (≥20%) were leukopenia anemia (30%), neutropenia (82%), and lymphopenia (35%), neutropenia (56%), and lymphopenia (52%). In (71%). IMPORTANT SAFETY INFORMATION relapsed/refractory patients, serious adverse reactions DARZALEX® as monotherapy: The most frequently (≥2% compared to Rd) were pneumonia (12%), upper reported adverse reactions (≥20%) were infusion respiratory tract infection (7%), influenza (3%), and pyrexia reactions (48%), fatigue (39%), nausea (27%), back pain (3%), and treatment-emergent Grade 3-4 hematology (23%), pyrexia (21%), cough (21%), and upper respiratory laboratory abnormalities (≥20%) were neutropenia (53%)

tract infection (20%). The overall incidence of serious and lymphopenia (52%). adverse reactions was 33%. The most frequent serious DARZALEX® in combination with bortezomib, melphalan, adverse reactions were pneumonia (6%), general and prednisone (DVMP): The most frequently reported physical health deterioration (3%), and pyrexia (3%). ADMINISTRATION adverse reactions (≥20%) were upper respiratory tract Treatment-emergent Grade 3-4 hematology laboratory infection (48%), infusion reactions (28%), and peripheral abnormalities (≥20%) were lymphopenia (40%) and edema (21%). Serious adverse reactions (≥2% compared neutropenia (20%). to the VMP arm) were pneumonia (11%), upper respiratory tract infection (5%), and pulmonary edema Please click here for DARZALEX® (2%). Treatment-emergent Grade 3-4 hematology full Prescribing Information. laboratory abnormalities (≥20%) were lymphopenia (58%), INFUSION RATES neutropenia (44%), and thrombocytopenia (38%). & REACTIONS cp-60862v3 DARZALEX® in combination with bortezomib and dexamethasone (DVd): The most frequently reported adverse reactions (≥20%) were peripheral sensory neuropathy (47%), infusion reactions (45%), upper respiratory tract infection (44%), diarrhea (32%), cough (27%), peripheral edema (22%), and dyspnea (21%). The PRE-/POST-INFUSION overall incidence of serious adverse reactions was 42%. MEDICATIONS Serious adverse reactions (≥2% compared to Vd) were upper respiratory tract infection (5%), diarrhea (2%), and atrial fibrillation (2%). Treatment-emergent Grade 3-4 hematology laboratory abnormalities (≥20%) were lymphopenia (48%) and thrombocytopenia (47%). CHECKLIST

49 DR d DARZALEX® (daratumumab) 1 administration Preparation for administration (cont’d) DVT d

• If not used immediately, the diluted solution can Preparation for administration1 be stored prior to administration for up to 24 hours

at refrigerated conditions, 2°C to 8°C (36°F DVMP Prepare the solution for infusion using aseptic to 46°F), and protected from light. Do not freeze technique as follows:

• Calculate the dose (mg), total volume (mL) DV d of DARZALEX® solution required, and the number of DARZALEX® vials needed based on the patient’s actual body weight Select Important Safety Information

® DP d • Check that the DARZALEX solution is colorless Adverse Reactions – The most frequently reported to pale yellow. Do not use if opaque particles, adverse reactions (incidence ≥20%) were: infusion discoloration, or foreign particles are present reactions, neutropenia, thrombocytopenia, fatigue,

• Remove a volume of 0.9% Sodium Chloride asthenia, nausea, diarrhea, constipation, decreased MONOTHERAPY Injection, USP, from the infusion bag/container appetite, vomiting, muscle spasms, arthralgia, back that is equal to the required volume of DARZALEX® pain, pyrexia, chills, dizziness, insomnia, cough, dyspnea, solution peripheral edema, peripheral sensory neuropathy, • Withdraw necessary amount of DARZALEX® bronchitis, pneumonia and upper respiratory tract solution and dilute to appropriate volume by infection. ® adding to the infusion bag/container containing DARZALEX in combination with lenalidomide and IMPORTANT SAFETY 0.9% Sodium Chloride Injection, USP. Infusion dexamethasone (DRd): The most frequent (≥20%) adverse INFORMATION bags/containers must be made of either reactions for newly diagnosed or relapsed refractory polyvinylchloride (PVC), polypropylene (PP), patients were, respectively, infusion reactions (41%, 48%), polyethylene (PE), or polyolefin blend (PP+PE). diarrhea (57%, 43%), nausea (32%, 24%), fatigue (40%,

Dilute under appropriate conditions. Discard 35%), pyrexia (23%, 20%), upper respiratory tract infection any unused portion left in the vial (52%, 65%), muscle spasms (29%, 26%), dyspnea (32%, • Gently invert the bag/container to mix the 21%), and cough (30%, 30%). In newly diagnosed patients, ADMINISTRATION solution. Do not shake constipation (41%), peripheral edema (41%), back pain (34%), asthenia (32%), bronchitis (29%), pneumonia • Parenteral drug products should be inspected (26%), decreased appetite (22%), and peripheral sensory visually for particulate matter and discoloration neuropathy (24%) were also reported. prior to administration, whenever solution and container permit. The diluted solution INFUSION RATES may develop very small, translucent to white & REACTIONS proteinaceous particles, as daratumumab is a protein. Do not use if visibly opaque particles, discoloration, or foreign particles are observed

• Since DARZALEX® does not contain a preservative,

administer the diluted solution immediately at PRE-/POST-INFUSION room temperature, 15°C to 25°C (59°F to 77°F), MEDICATIONS and in room light. Diluted solution may be kept at room temperature for a maximum of 15 hours (including infusion time)

Please see Indications and full Important Safety Information on pages 46-49 CHECKLIST and click here for DARZALEX® full Prescribing Information. 51 DR d DARZALEX® (daratumumab) Select Important Safety Information

administration (cont’d) Adverse Reactions (cont’d) – In newly diagnosed DVT d patients, serious adverse reactions (≥2% compared to Rd) were dehydration (2%), bronchitis (4%), and Administration1 pneumonia (15%), and treatment-emergent Grade 3-4 hematology laboratory abnormalities (≥20%) were DVMP • If stored in the refrigerator, allow the solution leukopenia (35%), neutropenia (56%), and lymphopenia to come to room temperature. Administer (52%). In relapsed/refractory patients, serious adverse diluted solution by intravenous (IV) infusion reactions (≥2% compared to Rd) were pneumonia DV d using an infusion set fitted with a flow regulator (12%), upper respiratory tract infection (7%), influenza and with an in-line, sterile, nonpyrogenic, low (3%), and pyrexia (3%), and treatment-emergent Grade protein-binding polyethersulfone (PES) filter 3-4 hematology laboratory abnormalities (≥20%) were

(pore size 0.22 or 0.2 micrometer). Administration neutropenia (53%) and lymphopenia (52%). DP d sets must be made of either polyurethane (PU), DARZALEX® in combination with bortezomib, melphalan, polybutadiene (PBD), PVC, PP, or PE and prednisone (DVMP): The most frequently reported • Do not store any unused portion of the infusion adverse reactions (≥20%) were upper respiratory tract solution for reuse. Any unused product or waste infection (48%), infusion reactions (28%), and peripheral MONOTHERAPY material should be disposed of in accordance edema (21%). Serious adverse reactions (≥2% compared with local requirements to the VMP arm) were pneumonia (11%), upper respiratory tract infection (5%), and pulmonary edema • Do not infuse DARZALEX® concomitantly in the (2%). Treatment-emergent Grade 3-4 hematology same IV line with other agents laboratory abnormalities (≥20%) were lymphopenia

(58%), neutropenia (44%), and thrombocytopenia (38%). IMPORTANT SAFETY DARZALEX® in combination with bortezomib and INFORMATION dexamethasone (DVd): The most frequently reported adverse reactions (≥20%) were peripheral sensory neuropathy (47%), infusion reactions (45%), upper respiratory tract infection (44%), diarrhea (32%), cough (27%), peripheral edema (22%), and dyspnea (21%). The overall incidence of serious adverse reactions was 42%. ADMINISTRATION Serious adverse reactions (≥2% compared to Vd) were upper respiratory tract infection (5%), diarrhea (2%), and atrial fibrillation (2%). Treatment-emergent Grade 3-4 hematology laboratory abnormalities (≥20%) were lymphopenia (48%) and thrombocytopenia (47%). INFUSION RATES & REACTIONS

PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 CHECKLIST and click here for DARZALEX® full Prescribing Information. 53 DR d Infusion rates for Select Important Safety Information ® DARZALEX (daratumumab) CONTRAINDICATIONS DVT d ® Slower rate of infusion for the first DARZALEX dose DARZALEX® (daratumumab) is contraindicated in patients is recommended, as infusion reactions are more with a history of severe hypersensitivity (eg, anaphylactic 1 likely to occur with the first infusion reactions) to daratumumab or any of the components of DVMP the formulation. Dilution Initial rate Rate Maximum volume (first hour) increment* rate WARNINGS AND PRECAUTIONS Week 1 infusion ® Infusion Reactions – DARZALEX can cause severe DV d

Option 1 (Single dose infusion) and/or serious infusion reactions, including anaphylactic reactions. In clinical trials, approximately half of all Week 1 Day 1 50 mL/hour 1000 mL 50 mL/hour 200 mL/hour patients experienced an infusion reaction. Most infusion (16 mg/kg) every hour* reactions occurred during the first infusion and were DP d Option 2 (Split dose infusion) Grade 1-2. Infusion reactions can also occur with

Week 1 Day 1 50 mL/hour subsequent infusions. Nearly all reactions occurred during 500 mL 50 mL/hour 200 mL/hour (8 mg/kg) every hour* infusion or within 4 hours of completing DARZALEX®. Prior to the introduction of post-infusion medication in MONOTHERAPY Week 1 Day 2 50 mL/hour 500 mL 50 mL/hour 200 mL/hour (8 mg/kg) every hour* clinical trials, infusion reactions occurred up to 48 hours after infusion. Severe reactions have occurred, including Week 2 50 mL/hour 500 mL 50 mL/hour 200 mL/hour (16 mg/kg) infusion† every hour* bronchospasm, hypoxia, dyspnea, hypertension, laryngeal edema, and pulmonary edema. Signs and Subsequent 100 mL/ 50 mL/hour (Week 3 onwards, 500 mL 200 mL/hour symptoms may include respiratory symptoms, such as ‡ hour every hour* 16 mg/kg) infusions nasal congestion, cough, throat irritation, as well as chills, IMPORTANT SAFETY vomiting, and nausea. Less common symptoms were INFORMATION *Consider incremental escalation of the infusion rate only in the absence of infusion reactions. wheezing, allergic rhinitis, pyrexia, chest discomfort, †Use a dilution volume of 500 mL for the 16 mg/kg dose only if there pruritus, and hypotension. were no infusion reactions the previous week. Otherwise, use a dilution volume of 1000 mL. ‡Use a modified initial rate (100 mL/hour) for subsequent infusions (ie, Week 3 onwards) only if there were no infusion reactions during the

previous infusion. Otherwise, use instructions indicated in the table ADMINISTRATION for the Week 2 infusion rate. • To facilitate administration, the first prescribed 16 mg/kg dose at Week 1 may be split over 2 consecutive days, ie, 8 mg/kg on Day 1 and Day 2, respectively (see above table)

§ INFUSION RATES

Median durations of 16 mg/kg infusions decreased & REACTIONS after the first infusion across all trials (N=1530)1,5 • First week infusion was 7 hours

• Second week infusion was 4 hours • Subsequent infusions were 3 hours PRE-/POST-INFUSION §

When the first dose was administered as 2 infusions over 2 days (split MEDICATIONS dose) in the EQUULEUS study (n=97), the median durations of infusions were 4.2 hours for Week 1 Day 1, 4.2 hours for Week 1 Day 2, 4.1 hours for Week 2, and 3.4 hours for the subsequent infusions.5|| || Median infusion length for subsequent infusions (Week 2+ in aggregate). Administer the Week 2 (16 mg/kg) infusion according to the infusion ®

rates outlined in Table 4 of the DARZALEX full Prescribing Information. Please see Indications and full Important Safety Administration of pre- and post-infusion Information on pages 46-49 CHECKLIST medications is recommended to reduce the and click here for DARZALEX® 1 risk of infusion reactions (see pages 61-62) full Prescribing Information. 55 DR d In clinical trials (monotherapy and combination treatments; N=1530) Infusion reactions by week (N2,066)1 DVT d Most infusion reactions occurred during the first infusion1 DVMP • For 40% of patients, infusion reactions (any grade) occurred with the first infusion, 2% of patients with the second infusion, and cumulatively, 4% of 1

patients with subsequent infusions DV d • The median time to onset of an infusion reaction was 1.5 hours (range: 0 to 72.8 hours)1

• Incidence of infusion modification due to reactions DP d was 37%1 • DARZALEX® can cause severe infusion reactions. Severe infusion reactions included bronchospasm, dyspnea, laryngeal edema, pulmonary edema, MONOTHERAPY hypoxia, and hypertension. Other adverse infusion reactions included nasal congestion, cough, chills, 1 throat irritation, vomiting, and nausea % • For infusion reactions of any grade/severity, 40 immediately interrupt the DARZALEX® infusion and manage symptoms. Management of infusion IMPORTANT SAFETY INFORMATION reactions may further require reduction in the rate of infusion, or permanent discontinuation of DARZALEX® for Grade 4 reactions1 Incidence of infusion reactions any grade (%) 4% Select Important Safety Information 2% ADMINISTRATION Infusion Reactions (cont’d) – Pre-medicate patients ee ee seet with antihistamines, antipyretics, and corticosteroids. sos Frequently monitor patients during the entire infusion. Interrupt infusion for reactions of any severity and institute medical management as needed. Permanently *Cumulative incidence over subsequent infusions. discontinue therapy if an anaphylactic reaction or INFUSION RATES life-threatening (Grade 4) reaction occurs and institute & REACTIONS appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re- starting the infusion.

PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 CHECKLIST and click here for DARZALEX® full Prescribing Information. 57 DR d Management of infusion reactions Select Important Safety Information

Infusion reactions of any grade or severity CONTRAINDICATIONS DVT d may be managed by interruption, modification, DARZALEX® (daratumumab) is contraindicated in and/or discontinuation of the infusion1 patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the • For infusion reactions of any grade/severity, DVMP immediately interrupt the DARZALEX® infusion components of the formulation. and manage symptoms. Management of infusion WARNINGS AND PRECAUTIONS reactions may further require reduction in the Infusion Reactions – DARZALEX® can cause severe rate of infusion or treatment discontinuation of DV d and/or serious infusion reactions, including anaphylactic DARZALEX® as outlined below reactions. In clinical trials, approximately half of all patients experienced an infusion reaction. Most

infusion reactions occurred during the first infusion DP d and were Grade 1-2. Infusion reactions can also occur with subsequent infusions. Nearly all reactions occurred during infusion or within 4 hours of completing ® DARZALEX . Prior to the introduction of post-infusion MONOTHERAPY medication in clinical trials, infusion reactions occurred up to 48 hours after infusion. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, laryngeal edema, and pulmonary edema. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well IMPORTANT SAFETY

as chills, vomiting, and nausea. Less common symptoms INFORMATION were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypotension. Pre-medicate patients with antihistamines, antipyretics,

and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt infusion for reactions of any

severity and institute medical management as needed. ADMINISTRATION Permanently discontinue therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion. INFUSION RATES

To reduce the risk of delayed infusion reactions, & REACTIONS administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long- PRE-/POST-INFUSION

acting bronchodilators and inhaled corticosteroids for MEDICATIONS patients with chronic obstructive pulmonary disease.

Please see Indications and full Important Safety Information on pages 46-49 CHECKLIST and click here for DARZALEX® full Prescribing Information. 59 DR d

Important information before Pre-infusion medications1 ® administering DARZALEX (daratumumab) DVT d To reduce the risk of infusion reactions, administer Interference with serological testing1 to all patients approximately 1 to 3 hours prior to • DARZALEX® binds to CD38 found on red blood cells every infusion as follows: (RBCs) and results in a positive Indirect Antiglobulin Dexamethasone 20 mg prior to every DVMP Test (Indirect Coombs test) that may persist for up to DARZALEX® infusion. When dexamethasone 6 months after the last DARZALEX® infusion is the background regimen-specific corticosteroid, the dexamethasone treatment dose will also serve as premedication on DV d Reminders DARZALEX® infusion days* During monotherapy, methylprednisolone Type and screen patients before starting DARZALEX® 100 mg, or equivalent, administered intravenously. DP d Inform blood banks when a patient is taking DARZALEX® Following the second infusion, the dose of Identify any DARZALEX®-treated blood samples corticosteroid may be reduced (oral or intravenous methylprednisolone 60 mg)

Ask patients to tell other healthcare professionals MONOTHERAPY that they have taken DARZALEX® Oral antipyretics (acetaminophen 650 to 1000 mg), plus Prophylaxis for herpes zoster reactivation1 Oral or IV antihistamine (diphenhydramine 25 to 50 mg or equivalent) • Initiate antiviral prophylaxis to prevent herpes zoster *Dexamethasone is given intravenously prior to the first reactivation within 1 week of starting DARZALEX® DARZALEX® infusion and oral administration may be

and continue for 3 months following treatment considered prior to subsequent infusions. Additional IMPORTANT SAFETY background regimen-specific corticosteroids INFORMATION (eg, prednisone) should not be taken on DARZALEX® Select Important Safety Information infusion days when patients receive dexamethasone (or equivalent) as pre-medication. Adverse Reactions – The most frequently reported adverse

reactions (incidence ≥20%) were: infusion reactions, neutropenia, thrombocytopenia, fatigue, asthenia, Select Important Safety Information

nausea, diarrhea, constipation, decreased appetite, ADMINISTRATION Interference With Serological Testing – Daratumumab vomiting, muscle spasms, arthralgia, back pain, pyrexia, binds to CD38 on red blood cells (RBCs) and results in chills, dizziness, insomnia, cough, dyspnea, peripheral a positive Indirect Antiglobulin Test (Indirect Coombs edema, peripheral sensory neuropathy, bronchitis, test). Daratumumab-mediated positive indirect pneumonia and upper respiratory tract infection. antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to INFUSION RATES

RBCs masks detection of antibodies to minor antigens & REACTIONS in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological

testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to ® PRE-/POST-INFUSION

starting DARZALEX . MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 CHECKLIST and click here for DARZALEX® full Prescribing Information. 61 DR d Post-infusion medications are Notes:

recommended DVT d

Post-infusion medications1 DVMP To reduce the risk of delayed infusion reactions, administer the day after every infusion as follows:

Oral corticosteroid (≤20 mg methylprednisolone DV d or equivalent); however, if a background regimen-specific corticosteroid (eg, dexamethasone, prednisone) is administered the day after the DARZALEX® infusion, DP d additional post-infusion medications may not be needed

During monotherapy, administer oral MONOTHERAPY corticosteroid (20 mg methylprednisolone or equivalent dose of an intermediate-acting or long-acting corticosteroid in accordance with local standards) on each of the 2 days following all DARZALEX® infusions (beginning the day after the infusion) IMPORTANT SAFETY

Note: For patients with a history of chronic obstructive INFORMATION pulmonary disorder, consider including short- and long- acting bronchodilators and inhaled corticosteroids. Following the first 4 infusions, if the patient experiences no major infusion reactions, these additional inhaled post- infusion medications may be discontinued.

ADMINISTRATION Select Important Safety Information Interference With Determination of Complete Response – Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE)

assays used for the clinical monitoring of endogenous INFUSION RATES M-protein. This interference can impact the determination & REACTIONS of complete response and of disease progression in some patients with IgG kappa myeloma protein.

PRE-/POST-INFUSION MEDICATIONS

Please see Indications and full Important Safety Information on pages 46-49 CHECKLIST and click here for DARZALEX® full Prescribing Information. 63 DR d Infusion checklist Administer pre- and post-infusion medications Initiate antiviral prophylaxis to prevent herpes DVT d Pre-infusion education zoster reactivation within 1 week of starting DARZALEX® and continue for 3 months following Schedule patients to allow for adequate treatment1

chair time Administer pre-infusion medications DVMP approximately 1–3 hours prior to every infusion to Confirm appropriate infusion set is stocked reduce the risk of infusion reactions1 — See pages 50–52 for additional details — Refer to page 61 for guidelines

Explain length of infusion and suggest that Administer post-infusion medications to reduce DV d 1 patients bring activities to occupy themselves the risk of delayed infusion reactions during their infusion — Refer to page 62 for guidelines

Provide a patient brochure and walk the Review safety information DP d patient through all important details Provide the patient with a comfort kit If a newly diagnosed, transplant-ineligible patient is receiving DARZALEX® + Revlimid® (lenalidomide) +

Discuss Important Safety Information dexamethasone (DRd), refer to pages 5–10 MONOTHERAPY Inform patients about Janssen CarePath and If a patient is receiving DARZALEX® + Revlimid® what services it provides (lenalidomide) + dexamethasone (DRd) after a prior regimen, refer to pages 11–16 — Call: 1-844-55DARZA (1-844-553-2792) If a patient is receiving DARZALEX® (daratumumab) + or visit JanssenCarePath.com/DARZALEX bortezomib + thalidomide + dexamethasone (DVTd), — Identifying cost support options that refer to pages 17-22

® ® IMPORTANT SAFETY

may help manage out-of-pocket costs If a patient is receiving DARZALEX + Velcade INFORMATION for DARZALEX® (daratumumab) (bortezomib) + melphalan + prednisone (DVMP), refer to pages 23–28 — Visit JanssenPrescriptionAssistance.com/ If a patient is receiving DARZALEX® + bortezomib + DARZALEX dexamethasone (DVd), refer to pages 29–34 If a patient is receiving DARZALEX® + Pomalyst® Discuss interference with serological testing (pomalidomide) and dexamethasone (DPd), after prior treatment, refer to pages 35–40 ADMINISTRATION If a patient is receiving DARZALEX® as a ® Explain that DARZALEX can affect blood test monotherapy, refer to pages 41–45 1 results used to match their blood for transfusions Monitor patient during the infusion process and Give the patient an Assay Interference Bracelet assess for adverse reactions1 and Card — Refer to pages 56–58 for more information INFUSION RATES

Type and screen patients before starting & REACTIONS Select Important Safety Information DARZALEX®1 Inform blood banks when a patient is Interference With Serological Testing – Daratumumab on DARZALEX®1 binds to CD38 on red blood cells (RBCs) and results in a

Identify any DARZALEX®-treated blood samples positive Indirect Antiglobulin Test (Indirect Coombs test).

Daratumumab-mediated positive indirect antiglobulin test PRE-/POST-INFUSION Ask patients to tell other healthcare may persist for up to 6 months after the last daratumumab MEDICATIONS ® professionals that they have taken DARZALEX infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type

Please see Indications are not impacted. Notify blood transfusion centers of this and full Important Safety interference with serological testing and inform blood Information on pages 46-49 ® banks that a patient has received DARZALEX . Type and CHECKLIST and click here for DARZALEX® screen patients prior to starting DARZALEX®. full Prescribing Information. 65 We can help make it simple for you to help your patients Janssen CarePath is your one source for access, affordability, and treatment support for your patients Janssen CarePath helps verify insurance coverage for your patients, provides reimbursement information, helps find financial assistance options for eligible patients, and provides ongoing support to help patients start and stay on DARZALEX®. Call a Janssen CarePath Care Coordinator at 877-CarePath (877-227-3728), Monday-Friday, 8:00 am to 8:00 pm ET Sign Up or Log In to the Provider Portal at JanssenCarePathPortal.com Visit JanssenCarePath.com

To contact Janssen Medical Information Phone: 1-800-Janssen (1-800-526-7736) E-mail: Submit questions via www.askjanssenmedinfo.com Search: www.JanssenMD.com Please see Indications and Important Safety Information on pages 46-49 and click here for DARZALEX® full Prescribing Information. References: 1. DARZALEX® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 2. Palumbo A, Chanan-Khan A, Weisel K, et al; the CASTOR Investigators. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(8):754-766. 3. Facon T, Kumar S, Plesner T, et al; the MAIA Trial Investigators. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104-2115. 4. Mateos MV, Dimopoulos MA, Cavo M, et al; the ALCYONE Trial Investigators. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378(6):518-528. 5. Data on file. Janssen Biotech, Inc. 6. Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016;387(10027):1551-1560. For more information, visit www.darzalexhcp.com