Clinical Applications of Newly Approved Drugs

INTERVIEWS Mikkael A. Sekeres, MD, MS: Clinical Applications of Newly Approved Drugs

Lisa K. Hicks, MD, MSc: The Promise and the Pitfalls of Quality Measures

CLINICAL NEWS Population Updates

Elotuzumab First and Only Immunostimulatory Antibody FDA- Approved for Multiple Myeloma

Differences in Treatment Patterns, Cost, and Quality Indicators by Site of Care ASH 2015

American Society of Hematology 57th Annual Meeting & Exposition December 5–8, 2015 Orlando, FL

Highlights & Insights for Managed Care Pharmacy Professionals ASH 2015 American Society of Hematology 57th Annual Meeting & Exposition December 5–8, 2015 • Orlando, FL

TABLE OF CONTENTS

Clinical News 06 ASH by the Numbers 07 Make the Change You Want to See 08 Population Updates 10 Elotuzumab First and Only Immunostimula- tory Antibody FDA-Approved for MM 10 First Results from a Pilot Phase 2 Study in Children with Primary HLH 11 Differences in Treatment Patterns, Cost, and Quality Indicators by Site of Care 13 Benefits of Patient-Reported Outcomes (PROs) for Clinicians, Patients, and Industry Interviews 09 Mikkael A. Sekeres, MD, MS: Clinical Ap- plications of Newly Approved Drugs 12 Lisa K. Hicks, MD, MSc: Exploring the Promise and the Pitfalls of Quality Measures

Media Highlights 08 Jill M. Johnson, MD: Guiding Hematologic Care with Genetic Testing 11 Griffin Rodgers, MD: Optimizing Therapy in Sickle Cell Disease

PUBLISHER ART DIRECTOR Gene Conselyea Ari Mihos WRITER/EDITOR PROJECT DIRECTOR Manda Frederick Renee Napoli 630 Madison Avenue 2nd Floor EDITORIAL SUPPORT

THE FIRST AND ONLY I UNO- STIMULATORY ANTIBODY INDICATED FOR THE TREATMENT OF ULTIPLE YELOMA in patients who had received 1 to 3 prior therapies

INDICATION EMPLICITI is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies. SELECTED IMPORTANT SAFETY INFORMATION Infusion Reactions • EMPLICITI can cause infusion reactions. Common symptoms include fever, chills, and hypertension. Bradycardia and hypotension also developed during infusions. In the trial, 5% of patients required interruption of the administration of EMPLICITI for a median of 25 minutes due to infusion reactions, and 1% of patients discontinued due to infusion reactions. Of the patients who experienced an infusion reaction, 70% (23/33) had them during the first dose. If a Grade 2 or higher infusion reaction occurs, interrupt the EMPLICITI infusion and institute appropriate medical and supportive measures. If the infusion reaction recurs, stop the EMPLICITI infusion and do not restart it on that day. Severe infusion reactions may require permanent discontinuation of EMPLICITI therapy and emergency treatment. • Premedicate with dexamethasone, H1 Blocker, H2 Blocker, and acetaminophen prior to infusing with EMPLICITI.

Rd=lenalidomide + dexamethasone. Please see additional Important Safety Information and Brief Summary of Prescribing Information for EMPLICITI on the following pages.

172002690.indd 1 12/9/15 2:12 PM For the treatment of ultiple yeloma in combination with Rd relative to Rd alone, EMPLICITI delivered A BENEFIT IN PFS THAT WAS AINTAINED OVER TI E1,2 in patients who had received 1 to 3 prior therapies Co-primary endpoints: PFS HR 0.70 [95% CI, 0.57, 0.85]; P=0.0004*; ORR† 78.5% with ERd [95% CI, 73.6, 82.9] vs 65.5% with Rd [95% CI, 60.1, 70.7]; =0.0002P 1‡

IMPORTANT SAFETY INFORMATION (continued) Infections • In a clinical trial of patients with multiple myeloma (N=635), infections were reported in 81.4% of patients in the EMPLICITI with lenalidomide/dexamethasone arm (ERd) and 74.4% in the lenalidomide/dexamethasone arm (Rd). Grade 3-4 infections were 28% (ERd) and 24.3% (Rd). Opportunistic infections were reported in 22% (ERd) and 12.9% (Rd). Fungal infections were 9.7% (ERd) and 5.4% (Rd). Herpes zoster was 13.5% (ERd) and 6.9% (Rd). Discontinuations due to infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd). Monitor patients for development of infections and treat promptly. Second Primary Malignancies • In a clinical trial of patients with multiple myeloma (N=635), invasive second primary malignancies (SPM) were 9.1% (ERd) and 5.7% (Rd). The rate of hematologic malignancies were the same between ERd and Rd treatment arms (1.6%). Solid tumors were reported in 3.5% (ERd) and 2.2% (Rd). Skin cancer was reported in 4.4% (ERd) and 2.8% (Rd). Monitor patients for the development of SPMs. Hepatotoxicity • Elevations in liver enzymes (AST/ALT greater than 3 times the upper limit, total bilirubin greater than 2 times the upper limit, and alkaline phosphatase less than 2 times the upper limit) consistent with hepatotoxicity were 2.5% (ERd) and 0.6% (Rd). Two patients experiencing hepatotoxicity discontinued treatment; however, 6 out of 8 patients had resolution and continued treatment. Monitor liver enzymes periodically. Stop EMPLICITI upon Grade 3 or higher elevation of liver enzymes. After return to baseline values, continuation of treatment may be considered. Interference with Determination of Complete Response • EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein. Pregnancy/Females and Males of Reproductive Potential • There are no studies with EMPLICITI with pregnant women to inform any drug associated risks. • There is a risk of fetal harm, including severe life-threatening human birth defects associated with lenalidomide and it is contraindicated for use in pregnancy. Refer to the lenalidomide full prescribing information for requirements regarding contraception and the prohibitions against blood and/or sperm donation due to presence and transmission in blood and/or semen and for additional information. Adverse Reactions • Infusion reactions were reported in approximately 10% of patients treated with EMPLICITI with lenalidomide and dexamethasone. All reports of infusion reaction were Grade 3 or lower. Grade 3 infusion reactions occurred in 1% of patients. • Serious adverse reactions were 65.4% (ERd) and 56.5% (Rd). The most frequent serious adverse reactions in the ERd arm compared to the Rd arm were: pneumonia (15.4%, 11%), pyrexia (6.9%, 4.7%), respiratory tract infection (3.1%, 1.3%), anemia (2.8%, 1.9%), pulmonary embolism (3.1%, 2.5%), and acute renal failure (2.5%, 1.9%). • The most common adverse reactions in ERd and Rd, respectively (>20%) were fatigue (61.6%, 51.7%), diarrhea (46.9%, 36.0%), pyrexia (37.4%, 24.6%), constipation (35.5%, 27.1%), cough (34.3%, 18.9%), peripheral neuropathy (26.7%, 20.8%), nasopharyngitis (24.5%, 19.2%), upper respiratory tract infection (22.6%, 17.4%), decreased appetite (20.8%, 12.6%), and pneumonia (20.1%, 14.2%).

Please see Brief Summary of Prescribing Information for EMPLICITI on the following pages.

172002690.indd 2 12/9/15 2:12 PM EMPLICITI + Rd: Progression-Free Survival (Minimum follow-up of 24 months)1

100 30% RELATIVE RISK REDUCTION % HR 0.70; 95% CI (0.57, 0.85) 90 68 P=0.0004* (Co-primary endpoint) 1-YEAR

(%) 80 PFS RATE 70 41% 60 2-YEAR PFS RATE 50 57% 40 30 20 %

Probability Progression-Free 27 10 EMPLICITI + Rd (n=321) Rd (n=325) 0 0 4 8 12 16 20 24 28 32 36 40 Progression-Free Survival (Months) Subjects at risk ERd 321 279 232 195 157 128 85 42 12 1 Rd 325 249 192 158 123 89 48 21 7

Significantly more patients responded to therapy with EMPLICITI in combination with Rd vs Rd alone1 At the time of this PFS analysis, there were fewer deaths in the ERd arm vs the Rd arm (94 [29%] vs 116 [36%])1

A Phase 3, randomized, open-label study conducted to evaluate the efficacy and safety of EMPLICITI in combination with Rd in 646 patients (EMPLICITI + Rd, n=321; Rd, n=325) with multiple myeloma who had received 1 to 3 prior therapies.1

*p-value based on the log-rank test stratified by ß2 microglobulins (<3.5 mg/L vs ≥3.5 mg/L), number of prior lines of therapy (1 vs 2 or 3), and prior immunomodulatory therapy (no vs prior thalidomide only vs other).1 †Assessed by blinded Independent Review Committee per European Group for Blood and Marrow Transplantation (EBMT) criteria.1 ‡p-value based on the Cochran-Mantel-Haenszel chi-square test stratified by ß2 microglobulins (<3.5 mg/L vs ≥3.5mg/L), number of prior lines of therapy (1 vs 2 or 3), and prior immunomodulatory therapy (no vs prior thalidomide only vs other).1 CI=confidence interval; HR=hazard ratio; ORR=overall response rate; PFS=progression-free survival; Rd=lenalidomide + dexamethasone. References: 1. EMPLICITI [package insert]. Princeton, NJ: Bristol-Myers Squibb Company. 2. Lonial S, Dimopoulos M, Palumbo A, et al; for the ELOQUENT-2 Investigators. N Engl J Med. Elotuzumab therapy for relapsed or refractory multiple myeloma. 2015;373(7):621–631.

Call 1-844-EMPLICITI NEW (1-844-367-5424)

Visit EmplicitiRx.com

172002690.indd 3 12/9/15 2:12 PM EMPLICITI™ (elotuzumab) for injection, for intravenous use • Second Primary Malignancies [see Warnings and Precautions]. Brief Summary of Prescribing Information. For complete prescribing information • Hepatotoxicity [see Warnings and Precautions]. consult official package insert. • Interference with Determination of Complete Response [see Warnings and Precautions]. INDICATIONS AND USAGE EMPLICITI (elotuzumab) is indicated in combination with lenalidomide and Clinical Trials Experience dexamethasone for the treatment of patients with multiple myeloma who have Because clinical trials are conducted under widely varying conditions, adverse received one to three prior therapies. reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates CONTRAINDICATIONS observed in practice. There are no contraindications to EMPLICITI. Because EMPLICITI is indicated for The safety data described in this section are based on a randomized, open- use in combination with lenalidomide and dexamethasone, healthcare providers should consult the prescribing information of these products for a complete label clinical trial in patients with previously treated multiple myeloma. In this description of contraindications before starting therapy. study, EMPLICITI (elotuzumab) 10 mg/kg was administered with lenalidomide and dexamethasone [see Clinical Studies (14) in full Prescribing Information]. WARNINGS AND PRECAUTIONS For adverse reaction evaluation, EMPLICITI combined with lenalidomide and Infusion Reactions dexamethasone was compared with lenalidomide and dexamethasone alone. EMPLICITI can cause infusion reactions. Infusion reactions were reported in The mean age of the population was 66 years and 57% of patients were 65 years approximately 10% of patients treated with EMPLICITI with lenalidomide and of age or older. Sixty percent (60%) of the population were male, 84% were white, dexamethasone in the randomized trial in multiple myeloma. All reports of infusion 10% were Asian, and 4% were black. The Eastern Cooperative Oncology Group reaction were Grade 3 or lower. Grade 3 infusion reactions occurred in 1% of (ECOG) performance status was 0 in 47%, 1 in 44%, and 2 in 9% of patients. patients. The most common symptoms of an infusion reaction included fever, chills, These data reflect exposure of 318 patients to EMPLICITI and 317 to control with a and hypertension. Bradycardia and hypotension also developed during infusions. median number of cycles of 19 for EMPLICITI and 14 for control. In the trial, 5% of patients required interruption of the administration of EMPLICITI for a median of 25 minutes due to infusion reactions, and 1% of patients Serious adverse reactions were reported in 65.4% of patients treated on the discontinued due to infusion reactions. Of the patients who experienced an EMPLICITI arm and 56.5% for patients treated on the control arm. The most infusion reaction, 70% (23/33) had them during the first dose. frequent serious adverse reactions in the EMPLICITI arm compared to the Administer premedication consisting of dexamethasone, antihistamines (H1 and control arm were: pneumonia (15.4% vs. 11%), pyrexia (6.9% vs. 4.7%), H2 blockers) and acetaminophen prior to EMPLICITI infusion [see Dosage and respiratory tract infection (3.1% vs. 1.3%), anemia (2.8% vs. 1.9%), pulmonary Administration (2.2) in full Prescribing Information]. embolism (3.1% vs. 2.5%), and acute renal failure (2.5% vs. 1.9%). Interrupt EMPLICITI infusion for Grade 2 or higher infusion reactions and institute The proportion of patients who discontinued any component of the treatment appropriate medical management [see Dosage and Administration (2.3) in full regimen due to adverse reactions as listed below was similar for both treatment Prescribing Information]. arms; 6.0% for patients treated on the EMPLICITI arm and 6.3% for patients Infections treated on the control. In a clinical trial of patients with multiple myeloma (N=635), infections were Adverse reactions occurring at a frequency of 10% or higher in the EMPLICITI reported in 81.4% of patients in the EMPLICITI combined with lenalidomide and arm and 5% or higher than the lenalidomide and dexamethasone arm for the dexamethasone (E-Ld) arm and 74.4% in lenalidomide and dexamethasone (Ld). randomized trial in multiple myeloma are presented in Table 1. Grade 3 to 4 infections were noted in 28% and 24.3% of E-Ld- and Ld-treated patients, respectively. Discontinuations due to infections occurred in 3.5% of E-Ld- Table 1: Adverse Reactions with a 10% or Higher Incidence for EMPLICITI-Treated Patients and a 5% or Higher Incidence than treated and 4.1% of Ld-treated patients. Fatal infections were reported in 2.5% Lenalidomide and Dexamethasone-Treated Patients [All Grades] and 2.2% of E-Ld- and Ld-treated patients. Opportunistic infections were reported in 22% of patients in the E-Ld arm and EMPLICITI + Lenalidomide and 12.9% of patients in the Ld arm. Fungal infections occurred in 9.7% of patients in Lenalidomide and Dexamethasone the E-Ld arm and 5.4% of patients in the Ld arm. Herpes zoster was reported in Dexamethasone 13.5% of patients treated with E-Ld and 6.9% of patients treated with Ld. Monitor N=318 N=317 patients for development of infections and treat promptly. Primary Term All Grades Grade 3/4 All Grades Grade 3/4 Second Primary Malignancies Fatigue* 61.6 12.6 51.7 11.7 In a clinical trial of patients with multiple myeloma (N=635), invasive second Diarrhea 46.9 5.0 36.0 4.1 primary malignancies (SPM) have been observed in 9.1% of patients treated with E-Ld and 5.7% of patients treated with Ld. The rate of hematologic malignancies Pyrexia 37.4 2.5 24.6 2.8 were the same between E-Ld and Ld treatment arms (1.6%). Solid tumors were Constipation 35.5 1.3 27.1 0.3 reported in 3.5% and 2.2% of E-Ld- and Ld-treated patients, respectively. Skin Cough† 34.3 0.3 18.9 0 cancer was reported in 4.4% and 2.8% of patients treated with E-Ld and Ld, Peripheral Neuropathy‡ 26.7 3.8 20.8 2.2 respectively. Monitor patients for the development of second primary malignancies. Nasopharyngitis 24.5 0 19.2 0 Hepatotoxicity Upper Respiratory Tract Infection 22.6 0.6 17.4 1.3 Elevations in liver enzymes (aspartate transaminase/alanine transaminase [AST/ALT] greater than 3 times the upper limit, total bilirubin greater than Decreased Appetite 20.8 1.6 12.6 1.3 2 times the upper limit, and alkaline phosphatase less than 2 times the upper Pneumonia§ 20.1 14.2 14.2 9.5 limit) consistent with hepatotoxicity were reported in 2.5% and 0.6% of E-Ld- Pain in Extremities 16.4 0.9 10.1 0.3 and Ld-treated patients in a clinical trial of patients with multiple myeloma Headache 15.4 0.3 7.6 0.3 (N=635). Two patients experiencing hepatotoxicity were not able to continue Vomiting 14.5 0.3 8.8 0.9 treatment; however, 6 out of 8 patients had resolution and were able to continue treatment. Monitor liver enzymes periodically. Stop EMPLICITI upon Grade 3 or Weight Decreased 13.8 1.3 6.0 0 higher elevation of liver enzymes. After return to baseline values, continuation of Lymphopenia 13.2 8.8 6.9 3.2 treatment may be considered. Cataracts 11.9 6.3 6.3 2.8 Interference with Determination of Complete Response Oropharyngeal Pain 10.1 0 4.4 0 EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected * The term fatigue is a grouping of the following terms: fatigue and asthenia. on both the serum protein electrophoresis (SPEP) and immunofixation (IFE) assays † used for the clinical monitoring of endogenous M-protein [see Drug Interactions]. The term cough is a grouping of the following terms: cough, productive cough, and upper This interference can impact the determination of complete response and possibly airway cough. ‡ The term peripheral neuropathy is a grouping of the following terms: peripheral relapse from complete response in patients with IgG kappa myeloma protein. neuropathy, axonal neuropathy, peripheral motor neuropathy, peripheral sensory ADVERSE REACTIONS neuropathy, and polyneuropathy.

The following adverse reactions are described in detail in other sections of the label: § The term pneumonia is a grouping of the following terms: pneumonia, atypical pneumonia, • Infusion reaction [see Warnings and Precautions]. bronchopneumonia, lobar pneumonia, bacterial pneumonia, fungal pneumonia, pneumonia influenza, and pneumococcal pneumonia. • Infections [see Warnings and Precautions].

172002690.indd 4 12/9/15 2:12 PM Other clinically important adverse reactions reported in patients treated with randomized trial in multiple myeloma. The detection of antibody formation is highly EMPLICITI (elotuzumab) that did not meet the criteria for inclusion in Table 1 but dependent on the sensitivity and specificity of the assay. Additionally, the observed occurred at a frequency of 5% or greater in the EMPLICITI group and at a frequency incidence of antibody (including neutralizing antibody) positivity in an assay may at least twice the control rate for the randomized trial in multiple myeloma are be influenced by several factors including assay methodology, sample handling, listed below: timing of sample collection, concomitant medications, and underlying disease. For General disorders and administration site conditions: chest pain these reasons, comparison of incidence of antibodies to EMPLICITI (elotuzumab) Immune system disorders: hypersensitivity with the incidences of antibodies to other products may be misleading. hypoesthesia Nervous system disorders: DRUG INTERACTIONS Psychiatric disorders: mood altered Skin and subcutaneous tissue disorders: night sweats Drug Interactions Laboratory abnormalities worsening from baseline and occurring at a frequency of No formal drug-drug interaction studies have been conducted with EMPLICITI. 10% or higher in the EMPLICITI group and 5% or higher than the lenalidomide and However, EMPLICITI is used in combination with lenalidomide and dexamethasone. dexamethasone group (criteria met for all Grades or Grade 3/4) for the randomized Refer to the prescribing information for those products for important drug- trial in multiple myeloma are presented in Table 2. drug interactions. Laboratory Test Interference Table 2: Laboratory Abnormalities Worsening from Baseline and with a 10% or Higher Incidence for EMPLICITI-Treated Patients and a 5% EMPLICITI may be detected in the SPEP and serum immunofixation assays of Higher Incidence than Lenalidomide and Dexamethasone-Treated myeloma patients and could interfere with correct response classification. A small Patients [Criteria met for All Grades or Grade 3/4] peak in the early gamma region on SPEP that is IgGƙ on serum immunofixation may potentially be attributed to EMPLICITI, particularly in patients whose EMPLICITI + Lenalidomide and Lenalidomide and Dexamethasone endogenous myeloma protein is IgA, IgM, IgD, or lambda light chain restricted. Dexamethasone This interference can impact the determination of complete response and possibly N=318 N=317 relapse from complete response in patients with IgG kappa myeloma protein . Laboratory Parameter All Grades Grade 3/4 All Grades Grade 3/4 [see Warnings and Precautions] USE IN SPECIFIC POPULATIONS Hematology Lymphopenia 99.4 76.7 98.4 48.7 Pregnancy Leukopenia 90.6 32.4 88.3 25.6 Risk Summary There are no studies with EMPLICITI with pregnant women to inform any Thrombocytopenia 83.6 19.2 77.8 20.3 drug associated risks. Animal reproduction studies have not been conducted Liver and Renal Function Tests with elotuzumab. Hypoalbuminemia 73.3 3.9 65.6 2.3 EMPLICITI is administered in combination with lenalidomide and dexamethasone. Lenalidomide can cause embryo-fetal harm and is contraindicated for use in Elevated Alkaline 38.7 1.3 29.8 0 pregnancy. Refer to the lenalidomide and dexamethasone prescribing information Phosphatase for additional information. Lenalidomide is only available through a REMS program. Chemistry The background risk in the U.S. general population of major birth defects is Hyperglycemia 89.3 17.0 85.4 10.2 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Hypocalcemia 78.0 11.3 76.7 4.7 Lactation Low Bicarbonate 62.9 0.4 45.1 0 Risk Summary There is no information on the presence of EMPLICITI in human milk, the Hyperkalemia 32.1 6.6 22.2 1.6 effect on the breast-fed infant, or the effect on milk production. Because of the potential for serious adverse reactions in breast-fed infants from Vital sign abnormalities were assessed by treatment arm for the randomized trial elotuzumab administered with lenalidomide/dexamethasone, breastfeeding is in multiple myeloma and are presented in Table 3. Percentages are based on not recommended. Refer to the lenalidomide and dexamethasone prescribing patients who had at least one on-treatment vital sign abnormality any time during information for additional information. the course of therapy. Females and Males of Reproductive Potential Table 3: Vital Sign Abnormalities Pregnancy Testing EMPLICITI + Lenalidomide and Refer to the lenalidomide labeling for pregnancy testing requirements prior to Lenalidomide and Dexamethasone initiating treatment in females of reproductive potential. Dexamethasone When EMPLICITI is used with lenalidomide, there is a risk of fetal harm, including N=318 N=317 severe life-threatening human birth defects associated with lenalidomide, and the Vital Sign Parameter % % need to follow requirements regarding pregnancy avoidance, including testing. Systolic Blood Pressure ≥160 mmHg 33.3 20.9 Contraception Diastolic Blood Pressure ≥100 mmHg 17.3 11.7 Refer to the lenalidomide labeling for contraception requirements prior to initiating treatment in females of reproductive potential and males. Systolic Blood Pressure <90 mmHg 28.9 8.2 Lenalidomide is present in the blood and semen of patients receiving the drug. Heart Rate ≥100 bpm 47.8 29.7 Refer to the lenalidomide full prescribing information for requirements regarding contraception and the prohibitions against blood and/or sperm donation due to Heart Rate <60 bpm 66 31.3 presence and transmission in blood and/or semen and for additional information. Immunogenicity Pediatric Use As with all therapeutic proteins, there is a potential for immunogenicity to EMPLICITI. Safety and effectiveness have not been established in pediatric patients. Of 390 patients across four clinical studies who were treated with EMPLICITI Geriatric Use and evaluable for the presence of anti-product antibodies, 72 patients (18.5%) tested positive for treatment-emergent anti-product antibodies by an Of the 646 patients across treatment groups in the randomized trial in multiple electrochemiluminescent (ECL) assay. In 63 (88%) of these 72 patients, anti- myeloma, 57% were 65 years of age or older; the number of patients 65 years product antibodies occurred within the first 2 months of the initiation of EMPLICITI or older was similar between treatment groups. No overall differences in efficacy treatment. Anti-product antibodies resolved by 2 to 4 months in 49 (78%) of these or safety were observed between patients 65 years or older and younger patients 63 patients. Neutralizing antibodies were detected in 19 of 299 patients in the (less than 65 years of age).

172002690.indd 5 12/9/15 2:12 PM OVERDOSAGE Infections The dose of EMPLICITI (elotuzumab) at which severe toxicity occurs is not known. • Inform patients of the risk of developing infections during treatment with EMPLICITI does not appear to be removed by dialysis as determined in a study of EMPLICITI (elotuzumab), and to report any symptoms of infection [see patients with renal impairment. Warnings and Precautions]. In case of overdosage, monitor patients closely for signs or symptoms of adverse reactions and institute appropriate symptomatic treatment. Second Primary Malignancies • Inform patients of the risk of developing SPM during treatment with EMPLICITI PATIENT COUNSELING INFORMATION [see Warnings and Precautions]. Advise the patient to read the FDA-approved patient labeling (Patient Information). Hepatotoxicity Infusion Reactions • EMPLICITI may cause infusion reactions. Advise patients to contact their • Inform patients of the risk of hepatotoxicity during treatment with EMPLICITI healthcare provider if they experience signs and symptoms of infusion and to report any signs and symptoms associated with this event to their reactions, including fever, chills, rash, or breathing problems within 24 hours healthcare provider for evaluation [see Warnings and Precautions]. of infusion [see Warnings and Precautions]. • Advise patients that they will be required to take the following oral medications prior to EMPLICITI dosing to reduce the risk of infusion reaction [see Dosage Manufactured by: and Administration (2.2) in full Prescribing Information]: Bristol-Myers Squibb Company • Dexamethasone orally as prescribed • H1 blocker: diphenhydramine or equivalent (if oral) Princeton, NJ 08543 USA • H2 blocker: ranitidine or equivalent (if oral) U.S. License No. 1713 • Acetaminophen (650-1000 mg orally) Pregnancy 1343639 Issued November 2015 • Advise patients that lenalidomide has the potential to cause fetal harm and has specific requirements regarding contraception, pregnancy testing, 689US1502988-03-01 blood and sperm donation, and transmission in sperm. Lenalidomide is only available through a REMS program [see Use in Specific Populations].

ASH By the Numbers

ASH 2015 The Need is in the Numbers at a Glance Sickle Cell Disease Blood Clots (deep vein (SCD)1: thrombosis and pulmo- • Affects70,000 to 100,000 Ameri- nary embolism)3: th cans 57 • 600,000 Americans affected each • 3 million Americans have sickle cell year; causes more deaths than annual session trait breast cancer and AIDS combined • During 2005, medical expenditures • #1 cause of maternal death in the U.S. for children with SCD averaged • 33% of patients will have a recur- $11,702 for children with Medicaid rence in 10 years 20,000 coverage and $14,772 for children with employer-sponsored insurance • $10 billion in related medical costs attendees in the U.S. each year 2 Leukemia : 2 • 54,000+ estimated new in cases in Myeloma : 3,000 2015 • 100,000 new cases each year presented abstracts • 300,000 people living with leuke- • 0.7% lifetime risk of being diag- mia in the U.S. nosed with multiple myeloma, based on 2010-2012 data • 24,000 deaths in 2015 • 89,658 people living with myeloma • 58% of people survive 5 years th in the U.S., in 2012 70 1. Sickle Cell Disease Association of America. sicklecelldisease.org. 2015. 2. National Cancer Institute. seer.cancer.gov/statfacts. birthday of Blood 2015. 3. Clot Connect. Clotconnect.org. March 29, 2014.

172002690.indd 6 12/9/15 2:12 PM ASH 2015

Make the Change You Getting It Right Want To See Precision Medicine, New Modifying Cells and Receptors for Therapies, and Industry Better Outcomes Evolutions ne of the key problems with choosing a care ne of the questions in focus at the 57th American pathway is that it is impossible to predict Hematology Society (ASH) Annual Meeting & O to what treatments people will respond—a OExposition was how to get it right—how to create single disorder or ailment may have a dozen different the right care path for the right patient, how to choose approved therapies that still, ultimately, act as blanket and use new therapies, and how to best collaborate as an therapies. Creating targeted therapies that address the industry to optimize health care. specific issue in each specific patient is ideal. “The ASH meet- Scores of sessions presented findings on ways to ing is internation- ally renowned not change or modify genetic expression to help cells do only for its diverse what they do best—attack malignancies, for ex- programming and ample—or inhibit the body from causing itself harm, high-caliber science, such as promoting malignant cell growth. The use of but also for its chimeric antigen receptor (CAR) T cells was of particu- unique ability to lar interest in many of the trials. foster collaboration James N. Kochenderfer, MD, and colleagues among hematolo- presented their efforts to improve the treatment of gists worldwide,” B-cell malignancies after allogeneic transplantation said ASH President by infusing allogeneic T cells that were genetically David A. Williams, MD, in his confer- modified to express an anti-CD19 CAR. The relapse ence welcoming. of malignancy is the key factor in the rate of death On working with in patients who have undergone allogeneic stem cell managed care transplantation because B-cell malignancies persist and professionals, Dr. are, consequently, treated with unmanipulated donor Williams said that David A. Williams, MD lymphocyte infusions; however, these donor infusions ASH will “continue may have inconsistent efficacy and can initiate morbid- to work with our ity and mortality from graft-versus-host disease. In colleagues in industry to make sure that we help to find targets for new drugs and help industry develop new their study, 20 patients with persistent malignancies drugs that will help our patients—to play a role with our (even after their allogenic transplantation) were given colleagues in industry, making sure our practitioners modified CAR T cells that were culled from the original understand, as new drugs come on line, how these can be transplant donor. Two weeks after the infusion of the applied most effectively to our patients.” modified cells, the participants showed a marked posi- The following pages feature conference highlights, from tive response. “Allogeneic anti-CD19 CAR T cells have targeted therapies to newly approved drugs to negotiating significant anti-malignancy activity when administered changing industry policies—all geared toward creating without prior chemotherapy,” said Dr. Kochender- the best possible health care system for patients. ● fer. “Malignancies that were resistant to allogeneic transplants and standard donor leukocyte infusions regressed after infusions of allogeneic anti-CD19 CAR T cells. [Moreover,] allogeneic anti-CD19 CAR T cells ASH will “continue to work with seem to be particularly effective against ALL and CLL.”1 our colleagues in industry.” Danhof and colleagues had similar success with CAR T cells for the treatment of multiple myeloma. —David A. Williams, MD The engineered T-cell receptors are able to “graft” a programmed preference onto an immune effec- tor cell, which can be deployed in the body toward

7 ASH 2015

an end—such as targeting tumor cells. Investigators Population Updates questioned what effect it may have on myeloma While blood may be one of the most common shared cells in engineering a T cell specifically for the target traits we have, there is an ever-evolving body of knowl- of another drug—in this case, the elotuzumab target edge showing that individual demographics require SLAMF7 (CS1, CD319). targeted and, in many cases, improved care. ASH 2015 “SLAMF7 is uniformly and highly expressed in was rich with research showing this to be true. Here are multiple myeloma (MM) where it promotes adhesion some of the findings. and survival of malignant plasma cells (mPCs) in Black pediatric patients with acute myeloid leukemia the bone marrow niche,” presented Sophia Danhof, present with more acute illness at initial diagnosis, ac- MD, study presenter. Elotuzumab, an anti-SLAMF7 counting for up to 63% of the relative excess induction monoclonal antibody (mAb), when used, has shown mortality. Identifying factors impacting acuity of illness at a reversible lymphodepletion and conferred potent presentation and associated with public insurance may anti-MM efficacy in combination therapy. Research- help to identify opportunities for intervention and thus nar- ers sought to evaluate whether SLAMF7-directed CAR row the current racial disparities in pediatric AML survival. engineered T cells could be generated from previously (Winestone et al. ABSTRACT #530.) treated MM patients, and to gauge the potency of the Older patients with acute myeloid leukemia (AML) have patient-generated T cells against mPCs. Their trial high health care cost utilization that reflects the bur- sought to generate SLAMF7 cells from both MM den of the disease, even with a decision to not receive patients and healthy donors. They were able to do so chemotherapy. Despite this population’s poor prognosis, from both, but were surprised to find that proportion palliative care and hospice services are rarely utilized. of SLAMF7+ cells was significantly higher in MM pa- Future work should study novel health care delivery tients compared to healthy participants. What’s more, models designed to meet the needs of this population. despite a high level of SLAMF7 expression on the (El-Jawahri et al. ABSTRACT #2126.) study population, T cells that expressed the SLAMF7- Women with sickle cell disease (SCD) have unmet con- CAR could be readily generated in all MM patients and traceptive needs, having limited knowledge about their extended to therapeutically relevant doses in a single obstetric risks, and this knowledge appears to come expansion cycle following enrichment.2 ● from their lived experience and provider counseling. (Whaley et al. ABSTRACT #3263.) 1. ABSTRACT #99. 2. ABSTRACT #115. Older adults with newly diagnosed multiple myeloma (25% of study patients) commonly experience falls. Falls are associated with more limited activity, depression, and jill m. johnson, md congestive heart failure. Prospective studies are needed to determine factors predictive of falls in order to target Guiding Hematologic Care with Genetic Testing interventions to those at high fall-risk and to prevent falls. (Wildes et al. ABSTRACT #4485.) “We have been doing, fundamentally, genetic testing for decades through our phenotyp- ing and through very low-resolution taping. Now, with the advent of scale sequencing and ar- rays, we can add to this information and bring it to the clinic. We have an advantage as a field because we know what to do with this genetic information as opposed to other fields where actionable variants are harder to identify.”

To watch the full interview with Jill M. Johnson, MD, scan the QR code or visit hematologydailyreport.amcp.org. Interview

8 Clinical Applications of Newly Approved Drugs An Interview with Mikkael A. Sekeres, MD, MS

n this interview, Rick McGuire, Executive Editor for centers to institute. And as was American Medical Communications, speaks with Mikkael the case with idarucizumab, I A. Sekeres, MD, MS, of the Cleveland Clinic, about three blinatumomab was approved newly approved drugs: idarucizumab, for the reversal of novel based on an accelerated approval oral anticoagulant (NOAC); blinatumomab, for the treatment pathway, which means that there of Philadelphia chromosome-negative relapsed or refractory is a phase 3 study with a more B-cell precursor acute lymphoblastic leukemia (R/R ALL); clinically meaningful endpoint— and panobinostat, for the treatment of patients with multiple so instead of just knowing the myeloma. response rate and durable response Mikkael A. Sekeres, MD, MS survival, we are waiting for the rick mcguire: What do we need to know about results of that phase 3 trial to come out. idarucizumab? mikkael a. sekeres, md: This is an interesting drug and an The third agent in your panel, panobinostat, was approved interesting indication. Dabigatran is an agent, of course, that is earlier this year for the treatment of patients with multiple used as an anticoagulant in patients who have atrial fibrillation, myeloma. There have been a variety of new agents or in patients who have had a blood clot. Sometimes, these approved for multiple myeloma. Where does this one fit in? patients are on an anticoagulant when something terrible Panobinostat is approved as part of combination therapy happens. In Cleveland, OH, they might be walking out on the based on interim markers of clinically meaningful benefits. sidewalk, slip on some ice, fall and hit their head, and develop So we are waiting an intracranial hemorrhage. They come to the emergency room for a phase 3 and, up until now, there hasn’t been an effective agent to reverse study with a more FDA-Approved Hematology that bleeding. We have one now in the form of idarucizumab, durable endpoint Therapies in 2015* and it’s a drug that works for urgent situations. to emerge. Sagar But one concern is that this is an expensive drug, and we Lonial, MD, who Parathyroid hormone: hormonal injection must first define what constitutes an emergency or urgent presented the for the control of hypocalcemia in patients indication for it. And then where are you going to stock it? data on this agent, with hypoparathyroidism. sees a role for A large institution like Cleveland Clinic, sure, we are going to Panobinostat: HDAC inhibitor for the treat- see these patients and we are going to stock the agent in our using this drug in ment of patients with multiple myeloma. main hospital. But if you’re at a smaller institution, is it worth combination with keeping this drug on the shelf when, eventually, it may expire bortezomib and Recombinant Factor VIII: intravenous and you’ll have to absorb the cost of that drug? dexamethasone in agent for the treatment of prophylaxis and treatment of hemophilia A. patients who have The second new agent, blinatumomab, is for the treatment failed a former Patiromer: polymer medicine that binds po- for Philadelphia chromosome-negative relapsed or immunologitory tassium for the treatment of hyperkalemia. refractory precursor B-cell acute lymphoblastic leukemia. drug. So he uses it Idarucizumab Impressions of this drug? in patients whom : urgent-care agent for the reversal of the anticoagulant effects of We’ve actually used this agent a lot. Blinatumomab is a monoclonal he thinks have a dabigatran. antibody that works in patients who do not have any drugs more proliferative approved for their diagnosis—acute lymphoblastic leukemia. We multiple myeloma. Ixazomib: oral proteasome inhibitor treat- can cure about 40% of these patients, but that means we can’t Even with the ment of multiple myeloma. for about 60%; all of those folks are destined to either relapse or cost of these new Elotuzumab: immunostimulatory anti- die. For these patients, we finally have a drug that’s approved that drugs, which can body for the treatment of multiple myeloma. really does work, and works for a durable period of time. complicate things, As with idarucizumab, one of the challenges with I am hopeful. ● Daratumumab: monoclonal antibody for blinatumomab is that it’s very expensive, and it requires an the treatment of multiple myeloma. inpatient stay, followed by a transition to outpatient care. *In order of approval date. Does not reflect all 2015 approved This has logistically been very challenging for a lot of cancer hematology drugs. Source: fda.gov.

9 ASH 2015

Elotuzumab First and Only Immunostimulatory Antibody FDA-Approved for Multiple Myeloma (MM)

atients with relapsed/refrac- in combination with lenalidomide and 0.57, 0.85; p = 0.0004]). Moreover, tory MM (RRMM) after one to dexamethasone in patients with RRMM. ELd showed a 79% overall response rate Pthree prior therapies can now be Patients (median age 66 years; 20% ≥75 ORR, compared with 66% in the Ld arm. treated with elotuzumab, an immunos- years old; median number of therapies 2; The most common adverse reactions timulatory monoclonal antibody (mAb) 35% refractory to their last therapy) with (≥20%) were fatigue, diarrhea, pyrexia, that recognizes Signaling Lymphocytic RRMM were randomized 1:1 to elotu- constipation, cough, peripheral neuropa- Activation Molecule F7 (SLAMF7), a zumab with lenalidomide/dexamethasone thy, nasopharyngitis, upper respiratory protein highly expressed by myeloma (ELd) or lenalidomide/dexamethasone tract infection, decreased appetite, and and natural killer cells. (Ld) alone in 28-day cycles until disease pneumonia, occurring, statistically, more Elotuzumab has a dual mechanism of progression or unacceptable toxicity. The in the ELd arm. action, directly activating natural killer co-primary endpoints were progression- “The addition of elotuzumab to Ld cells and initiating antibody-dependent free survival (PFS) and overall response led to an effective and durable benefit, cell-mediated cytotoxicity targeted rate (ORR), while overall survival and representing a novel approach to treat- against myeloma cells, with negligible health-related quality of life were also ing MM,” said presenters. “The updated effect on normal tissues. considered. safety and tolerability data reported Meletios A. Dimopoulos, MD, and The 2-year PFS interim analysis of were consistent with previous findings, colleagues shared the updated safety the trial revealed that ELd treatment confirming that there are minimal in- and efficacy follow-up results of the resulted in a 30% reduction in the risk cremental toxicities associated with the ELOQUENT-2 trial, a phase 3, random- of disease progression or death com- addition of elotuzumab.” ● ized, open-label study of elotuzumab pared with Ld alone (HR 0.70 [95% CI: ABSTRACT #653. late-breaker First Results from a Pilot Phase 2 Study in Children with Primary HLH

novel targeted approach to the treatment of Hemo- phagocytic Lymphohistiocytosis (HLH) with an A anti-interferon gamma (IFNγ) monoclonal antibody NI-0501 is a safe and effective (mAb), NI-0501, offers an innovative targeted and potentially therapeutic option in patients with less toxic approach to HLH management, according to the pilot phase 2 investigators. NI-0501 is a fully human, high affinity, pHLH who have demonstrated anti-IFNγ mAb that binds to and neutralizes human IFNγ, of- unsatisfactory response, or are fering a novel and targeted approach for the control of HLH. Primary HLH (pHLH) is a rare immune regulatory disorder intolerant, to conventional therapy. with complete mortality if untreated. The disorder is sustained by pathologic immune activation, initiating the development of fever, splenomegaly, cytopenias, and coagulopathy, which ulti- poietic stem cell transplant (allo-HSCT). Drug-related toxicities mately may cause multi-organ failure and death. The elevated contribute to the rate of death for those with HLH even with production of IFNγ is thought to be key in the development of increasingly intensified treatment regimens. the disease, based on data from murine models of primary and A total of 13 HLH patients (aged 2.5-13 years) were en- secondary HLH (sHLH). Observational studies in patients with rolled. Twelve patients received NI-0501 as a second line treat- HLH, immune-chemotherapy, primarily etoposide-based regi- ment after having received conventional therapy and either mens, is at present the only pharmacological approach able to reactivating, obtaining unsatisfactory response, or being intol- control HLH and bring patients to curative allogeneic hemato- erant to therapy. One patient was treated with NI-0501 in first

10 line. Most study participants had severe HLH, in compromised griffin rodgers, md general condition (two patients in ICU) and carrying significant Optimizing Therapy in Sickle Cell Disease toxicities from previous HLH treatments. “Overall, NI-0501 treatment significantly improved parameters of “This was the first HLH disease activity,” said Michael Jordan, MD, study presenter, “and disease to be under- nine of 13 patients achieved a satisfactory response. Seven patients stood at the molecular level—the first genetic have proceeded to allo-HSCT. Allo-HSCT is planned for two patients disease... So not only with good HLH control upon identification of an appropriate donor.” do we know the protein NI-0501 was well tolerated and no safety concerns were noted, abnormality, we also including infections caused by IFNγ neutralization or in those patients know this genetic who had not previously received chemotherapy, myelotoxicity, or hemo- underpinning, and we dynamic alterations. have ready access to the stem cells of these “The results of this study show that NI-0501 is a safe and effec- patients in the form of the bone marrow or the peripheral blood tive therapeutic option in patients with pHLH who have demon- cells. So treating the upstream complications strated unsatisfactory response, or are intolerant, to conventional is an area of investigation.” therapy. Furthermore, therapy with NI-0501 was not associated with any of the typical short- or long-term toxicities reported for To see the full interview with Griffin etoposide-based regimens. Assessment of NI-0501 as first line Rodgers, MD, scan the QR code or visit hematologydailyreport.amcp.org. treatment for pHLH is ongoing,” said Dr. Jordan. ● Interview conducted by Rick McGuire. LATE-BREAKING ABSTRACT #3.

Differences in Treatment Patterns, Cost, and Quality Indicators by Site of Care atients undergoing oncology infu- SOC attribution (HO vs. PO) was based • 24% higher total oncology-related sion therapy that occurs in physi- on where patients received ≥90% of their health care costs ($58,033) com- Pcian office (PO) settings instead of infusions. Health care costs were deter- pared with PO ($46,652). hospital outpatient (HO) settings may mined by the sum of plan and patient see treatment benefits. The rising trend costs for medical and pharmacy claims However, among those receiving che- of community-clinic acquisitions by hos- in the 6 months following the index date, motherapy only, treatment duration was pitals has led to an increase in therapies and considered oncology costs, including shorter in the HO setting with 78.5 days occurring in HO settings instead of a supportive care. vs. the PO setting with 112 days. In the PO. Recent studies have suggested that The results found many differences HO setting, there were fewer infusions differences between sites of care (SOC) between the infusion therapy duration for patients receiving chemotherapy and can impact cancer treatment delivery and treatment between PO and HO set- rituximab, and chemotherapy only. And and overall health care costs. Casebeer et tings. Those treated in HO settings had: there were no statistically significant dif- al. investigated, in this study, differences ferences in the quality of care indicators in treatment patterns, cost, and quality • A higher mean comorbidity index by SOC, including the use of infusions or of care among predominately Medicare, compared to PO patients, hospitalizations within 30 days of death (85%) patients with NHL/CLL receiving among Medicare patients. infusion chemotherapy and/or rituximab • An increased use of rituximab “As care shifts from the PO to HO set- in a HO versus PO setting. monotherapy, ting,” said Adrianne W. Casebeer, MPP, Using Humana medical claims data, MS, PhD, “future studies should assess study investigators identified 1,859 • An increased use of rituximab the impact of SOC on the delivery of care patients (≥18 years) who had been given with chemotherapy, and health care costs associated with cur- infusion therapy in 2008-12 with at least rent therapeutic options for NHL/CLL.” ● two claims with a diagnosis of NHL or • Higher health care costs ($60,536) CLL occurring 30 or more days apart. compared to PO setting ($49,800), ABSTRACT #3298. Photo: © 2015 ASH

11 ASH 2015

Exploring the Promise and the Pitfalls of Quality Measures An Interview with Lisa K. Hicks, MD, MSc

hile most agree that measuring and optimizing achieve, is a good thing. But how we the quality of medical care is vital, there has get to the next milestone of using W been controversy on the best way to do so. this quality improvement science, Rick McGuire, Executive Editor for American Medical and using metrics to bring about Communications, spoke with Lisa K. Hicks, MD, MSc, at St. positive change, is going to be the Michael’s Hospital and Asst. Professor at the University of more difficult one. Toronto, about some of these current and future changes. The story isn’t finished, like so many things in hematology. One rick mcguire: To start, why focus on quality measures? of the challenges in quality work is Lisa K. Hicks, MD, MSc lisa k. hicks, md, msc: Quality metrics are a core, that it is very contextual, so it isn’t foundational topic in quality-improvement sciences. I think clear if what works in one specific context works in a different it was W. Edwards Deming who said, “If you can’t measure context. it, you can’t manage it.” It is going to be increasingly important for our membership to have familiarity with What can be said to make people feel more comfortable quality metrics—specifically with pay-for-performance— with the direction of quality metrics? especially those members from the United States, where the I would tell them to learn. It is important for individual rate of change is extremely quick. It is no longer theoretical physicians to find out about the changes that are occurring. whether or not quality metrics are going to have an impact Large practices or practice groups should have a point on their practices; it is very real. person who is following the evolutions to make sure that they aren’t caught off guard, and to know how to adapt their practice. Then I would encourage physicians to remain optimistic and keep an eye on the big prize, which is It is no longer theoretical whether improved care for our patients. Are we going to get there easily? Probably not. We need or not quality metrics are going to physicians engaged, doing high-quality, innovative work, and have an impact on their practice; it pushing back. But not just physicians—other allied health workers and some of our non-physician academics need to be is very real. part of this dialogue as it moves forward. If we haven’t got the right quality metrics, if we do not think that the program that’s evolving is the right one, now is the time to speak up and start proposing new metrics and developing the science. ● If we want to have positive changes in medicine, we need valid metrics; this is not controversial. But how to establish a good quality metric, how to know when you’ve got one, that is more controversial. And how to use quality metrics to change practice in a positive way is really a new science; the evidence is evolving at the same rate as the changes are happening, which is a little bit unusual.

Change can be uncomfortable. Some concern has focused on the current quality programs and if they are heading in the right direction. What is the right direction? Can anybody say exactly what the right direction is? It is good that we are in a place in which everybody agrees that we need change—that’s probably a big accomplishment in and of itself. Acknowledging that measuring the quality of the work we

12 Benefits of Patient-Reported Outcomes (PROs) for Clinicians, Patients and Industry t is known that incorporating the patient perspective into cannot consider “cost” when considering approval). Moreover, health care is important—how to best do this was the focus the data submitted to the FDA for approval currently focus on Iof a special education program designated to explore how laboratory, radiography, and clinician-reported adverse events, PROs can be utilized into clinical care and research. Session despite the fact that some events can only be measured by moderator Ellen M. Werner, PhD, defined PRO as “the mea- patients. Patient-reported outcomes also do not affect product surement of a patient’s perspective of a health condition and its labeling, even though they clearly affect the patient. Kwitkows- treatment.” Examples would include “a patient’s report of func- ki argues that PROs have great potential to act as “guidance tion, pain or other symptoms, satisfaction, and sleep quality.” for the industry.” Many stakeholders are interested in under- David Cella, PhD, shared how PRO measurements are standing the patient’s experience, which can only lead to better developed, giving the Patient Reported Outcomes Measurement therapies that best serve those who use them. Information System (PROMIS), an NIH-funded program, as PROs have a practical use in a physician’s daily practice, an example. PROMIS is a web-based portal wherein patients as well, argues Julie A. Panepinto, MD, MSPH. At their self-report their health status using various response templates. most basic level, PROs are already used with shared expres- For physicians, the program creates a hub from which immedi- sions between physicians and patients. Notes like, “Patient is ate and updated PROs can be accessed to assist in diagnosis, doing fine” or “No concerns” are made in charts. This leaves therapy maintenance, etc. For researchers, PROMIS creates a great amount of room for missing what is really going on and validates instruments that measure the emotional state, with the patient, she argued. It is difficult to estimate patient function, and perceptions relevant to reported outcomes, function. An observational study revealed, for example, that even acting as primary or secondary endpoints in clinical health care providers did not identify 50% of symptoms in and observational studies of the effectiveness of treatment. A patients that were detected by a PRO measure; issues such special committee is being developed to work with industry as dyspnea, anorexia, pain, and insomnia were missed by members to explore how the PROMIS data can be used toward more than 60% of health care providers studied. The severi- pharmaceutical, biotechnology, medical devices, and diagnostic ty of a patient’s symptoms are often underestimated, as well. organizations. When compared, the clinician’s assessment of the patient How to use PROs for drug development was also discussed and the patient’s own PRO revealed roughly a 50% disagree- by Virginia E. Kwitkowski, MS, NP. Specifically, Kwitkowski ment rate. The benefits of using PROs in a clinical setting? spoke of using PROs to develop drugs with the FDA in mind. They could alert physicians to patient problems, monitor a The measures that the FDA currently uses take into account a patient’s function over time, facilitate communication, and patient’s survival, how a patient feels (in terms of health), and provide a patient with information on how they are doing how a patient functions after using a therapy. This, she argues, compared to patients who are similar to them. What’s more, is not enough, and a more modular approach is needed because with the rise of electronic medical health records, digitized therapies impact a patient in other “non-health” ways—qual- results from PROs can create a holistic picture that follows ity of life measurements, such as financial burden (the FDA each patient as they utilize the health care system. ● Photo: © 2015 ASH