NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend NCCN brentuximab vedotin (ADCETRIS®) + CHP as preferred regimen for the frontline 1 RECOMMENDATION treatment of CD30-expressing peripheral T-cell lymphomas (PTCL)
ADCETRIS+CHP IN FRONTLINE PTCL: FDA approved for any PTCL subtype with CD30 expression (≥1%)2
ADCETRIS is a CD30-directed antibody-drug conjugate indicated for treatment of adult patients with previously untreated sALCL or other CD30-expressing PTCL, including AITL and PTCL-NOS, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP).2 • ADCETRIS+CHP was studied in the following subtypes in the ECHELON-2 trial: sALCL ALK+/–, PTCL-NOS, AITL, ATLL, EATL, and HSTCL3
ECHELON-2 Trial Design: A multicenter, phase 3, randomized, double-blind, double-dummy, actively controlled trial in 452 patients with sALCL and other CD30-expressing PTCL. Patients were randomized 1:1 to A+CHP (n = 226) or CHOP (n = 226), and received treatment every 3 weeks for 6 to 8 cycles at investigator’s discretion. Primary endpoint was progression-free survival, defined as progression, death from any cause, or receipt of subsequent anticancer therapy to treat residual or progressive disease.2,3
Important Safety Information BOXED WARNING PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients. Contraindication ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
Please see additional Important Safety Information on page 4 and full Prescribing Information, including BOXED WARNING, at adcetrispro.com Patients with any PTCL subtype with CD30 expression ≥1% may be eligible for ADCETRIS2
Types of PTCL by CD30 expression
Uniform (nodal)4,5
sALCL ALK+ sALCL ALK–
Variable4,5
Nodal Cutaneous T-cell lymphoma Extranodal Leukemic/disseminated
PTCL-NOS Mycosis fungoides EATL T-cell prolymphocytic leukemia
T-cell large granular AITL Sézary syndrome ENKTL lymphocytic leukemia
Primary cutaneous PTCL, Aggressive PTCL-TFH * HSTCL rare subtypes NK-cell leukemia
Primary cutaneous Subcutaneous FTCL* CD30 + T-cell panniculitis-like ATLL lymphoproliferative disorder T-cell lymphoma
Primary Lymphomatoid Chronic lymphoproliferative cutaneous ALCL papulosis disorder of NK cells*
Systemic EBV+ —Adapted from Hsi et al, 2014, and Swerdlow et al, 2016. T-cell lymphoproliferative *Provisional entities.5 disorder of childhood
AITL = angioimmunoblastic T-cell lymphoma; ALCL = anaplastic large-cell lymphoma; ALK = anaplastic lymphoma kinase; ATLL = adult T-cell leukemia/lymphoma; EATL = enteropathy-associated T-cell lymphoma; EBV = Epstein-Barr virus; ENKTL = extranodal natural killer/T-cell lymphoma; FTCL = follicular T-cell lymphoma; HSTCL = hepatosplenic T-cell lymphoma; NK=natural killer; PTCL-NOS = peripheral T-cell lymphoma, not otherwise specified; PTCL-TFH = peripheral T-cell lymphoma T-follicular helper phenotype; sALCL = systemic anaplastic large-cell lymphoma.
Please see additional Important Safety Information on page 4 and full Prescribing Information, including 02 BOXED WARNING, at adcetrispro.com Ask pathologists to consistently report CD30 as a percentage for all subtypes
ADCETRIS® (brentuximab vedotin) is a CD30-directed therapy indicated for adult patients with previously untreated sALCL or other CD30-expressing PTCL in combination with cyclophosphamide, doxorubicin, and prednisone (CHP)2
• Expression of CD30 is reported inconsistently in pathology results (often binary, eg, positive/negative)6,7 • Eligible patients may be overlooked for treatment if the percentage expression is not reported
SAMPLE REPORT #1 SAMPLE REPORT #2 WITH BINARY RESULTS WITH PERCENT STATED Expression Expression Antibody detected in Antibody detected in tumor cells tumor cells
CD30 NEGATIVE CD30 1%
Patient eligible for ADCETRIS but may be overlooked with first report
PTCL = peripheral T-cell lymphoma; sALCL = systemic anaplastic large-cell lymphoma.
References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for T-Cell Lymphomas (V2.2019). © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed September 24, 2019. To view the most recent and complete version of the guidelines, go online to NCCN.org. 2. ADCETRIS [Prescribing Information]. Bothell, WA: Seattle Genetics, Inc. October 2019. 3. Horwitz S, O’Connor OA, Pro B, et al; for the ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019;393:229-240. 4. Hsi ED, Said J, Macon WR, et al. Diagnostic accuracy of a defined immunophenotypic and molecular genetic approach for peripheral T/NK-cell lymphomas. A North American PTCL study group project. Am J Surg Pathol. 2014;38:768-775. 5. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms.Blood. 2016;127:2375-2390. 6. Weisenburger DD, Savage KJ, Harris NL, et al. Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project. Blood. 2011;117:3402-3408. 7. Jacobsen ED, Sharman JP, Oki Y, et al. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015;125:1394-1402.
Please see additional Important Safety Information on page 4 and full Prescribing Information, including 03 BOXED WARNING, at adcetrispro.com Important Safety Information, cont’d Warnings and Precautions with some cases occurring within 3 months of initial exposure. ® In addition to ADCETRIS therapy, other possible contributory • Peripheral neuropathy (PN): ADCETRIS (brentuximab vedotin) factors include prior therapies and underlying disease that may causes PN that is predominantly sensory. Cases of motor PN have cause immunosuppression. Consider PML diagnosis in patients also been reported. ADCETRIS-induced PN is cumulative. Monitor with new-onset signs and symptoms of central nervous system for symptoms such as hypoesthesia, hyperesthesia, paresthesia, abnormalities. Hold ADCETRIS if PML is suspected and discomfort, a burning sensation, neuropathic pain, or weakness. discontinue ADCETRIS if PML is confirmed. Institute dose modifications accordingly. • Pulmonary toxicity: Fatal and serious events of noninfectious • Anaphylaxis and infusion reactions: Infusion-related reactions pulmonary toxicity, including pneumonitis, interstitial lung disease, (IRR), including anaphylaxis, have occurred with ADCETRIS. and acute respiratory distress syndrome, have been reported. Monitor patients during infusion. If an IRR occurs, interrupt the Monitor patients for signs and symptoms, including cough and infusion and institute appropriate medical management. If dyspnea. In the event of new or worsening pulmonary symptoms, anaphylaxis occurs, immediately and permanently discontinue hold ADCETRIS dosing during evaluation and until symptomatic the infusion and administer appropriate medical therapy. improvement. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an • Serious dermatologic reactions: Fatal and serious cases of antihistamine, and a corticosteroid. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, • Hematologic toxicities: Fatal and serious cases of febrile discontinue ADCETRIS and administer appropriate medical therapy. neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia • Gastrointestinal (GI) complications: Fatal and serious cases of or anemia can occur with ADCETRIS. acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, Administer G-CSF primary prophylaxis beginning with Cycle 1 intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. for patients who receive ADCETRIS in combination with Lymphoma with preexisting GI involvement may increase the risk chemotherapy for previously untreated Stage III/IV cHL or of perforation. In the event of new or worsening GI symptoms, previously untreated PTCL. including severe abdominal pain, perform a prompt diagnostic Monitor complete blood counts prior to each ADCETRIS dose. evaluation and treat appropriately. Monitor more frequently for patients with Grade 3 or 4 • Hyperglycemia: Serious cases, such as new-onset hyperglycemia, neutropenia. Monitor patients for fever. If Grade 3 or 4 exacerbation of preexisting diabetes mellitus, and ketoacidosis neutropenia develops, consider dose delays, reductions, (including fatal outcomes) have been reported with ADCETRIS. discontinuation, or G-CSF prophylaxis with subsequent doses. Hyperglycemia occurred more frequently in patients with high • Serious infections and opportunistic infections: Infections such body mass index or diabetes. Monitor serum glucose and if as pneumonia, bacteremia, and sepsis or septic shock (including hyperglycemia develops, administer anti-hyperglycemic fatal outcomes) have been reported in ADCETRIS-treated medications as clinically indicated. patients. Closely monitor patients during treatment for bacterial, • Embryo-fetal toxicity: Based on the mechanism of action and fungal, or viral infections. animal studies, ADCETRIS can cause fetal harm. Advise females • Tumor lysis syndrome: Closely monitor patients with rapidly of reproductive potential of the potential risk to the fetus, and to proliferating tumor and high tumor burden. avoid pregnancy during ADCETRIS treatment and for at least • Increased toxicity in the presence of severe renal impairment: 6 months after the final dose of ADCETRIS. The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to Most Common (≥20% in any study) Adverse Reactions patients with normal renal function. Avoid use in patients with Peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper severe renal impairment. respiratory tract infection, pyrexia, constipation, vomiting, alopecia, • Increased toxicity in the presence of moderate or severe hepatic decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, impairment: The frequency of ≥Grade 3 adverse reactions and and mucositis. deaths was greater in patients with moderate or severe hepatic Drug Interactions impairment compared to patients with normal hepatic function. Concomitant use of strong CYP3A4 inhibitors or inducers has the Avoid use in patients with moderate or severe hepatic impairment. potential to affect the exposure to monomethyl auristatin E (MMAE). • Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with Use in Specific Populations hepatocellular injury, including elevations of transaminases Moderate or severe hepatic impairment or severe renal impairment: and/or bilirubin, and occurred after the first ADCETRIS dose MMAE exposure and adverse reactions are increased. Avoid use. or rechallenge. Preexisting liver disease, elevated baseline liver Advise males with female sexual partners of reproductive potential enzymes, and concomitant medications may increase the risk. to use effective contraception during ADCETRIS treatment and for Monitor liver enzymes and bilirubin. Patients with new, at least 6 months after the final dose of ADCETRIS. worsening, or recurrent hepatotoxicity may require a delay, Advise patients to report pregnancy immediately and avoid change in dose, or discontinuation of ADCETRIS. breastfeeding while receiving ADCETRIS. • PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of Please see full Prescribing Information, including BOXED symptoms occurred at various times from initiation of ADCETRIS, WARNING, in pocket or at adcetrispro.com NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.
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