ASH

Highlights & Insights for Managed Care Pharmacy Professionals

American Society of Hematology57th Annual Meeting & ExpositionDecember 5–8, 2015 Orlando, FL

2015

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 NEWSPopulation Updates

Elotuzumab First and Only Immunostimulatory Antibody FDA-

Approved for Multiple Myeloma

Differences in Treatment Patterns, Cost, and Quality Indicators by

Site of Care

American Society of Hematology57th Annual Meeting & ExpositionDecember 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

ASH2015

PUBLISHERGene Conselyea

WRITER/EDITORManda Frederick

EDITORIAL SUPPORTNeal Learner

630 Madison Avenue2nd FloorManalapan, NJ 07726 ©2015 American Medical Communications, Inc, Manalapan, NJ 07726. PR15-026

ART DIRECTORAri Mihos

PROJECT DIRECTORRenee Napoli

Pho

to: ©

20

15 A

SH

NOW APPROVED in combination with Rd

I UNO- STIMULATORYTHE FIRST AND ONLY

ANTIBODY INDICATED FOR THE TREATMENT OF ULTIPLE YELOMAin patients who had received 1 to 3 prior therapies

INDICATIONEMPLICITI 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 INFORMATIONInfusion 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.

Please see additional Important Safety Information and Brief Summary of Prescribing Information for EMPLICITI on the following pages.

Rd=lenalidomide + dexamethasone.

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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.

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]; P=0.00021‡

in patients who had received 1 to 3 prior therapies

For the treatment of ultiple yeloma in combination with Rd relative to Rd alone, EMPLICITI delivered

A BENEFIT IN PFS THAT WAS AINTAINEDOVER TI E1,2

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100

90

80

70

60

50

40

30

20

10

0

EMPLICITI + Rd: Progression-Free Survival (Minimum follow-up of 24 months)1

ERd

Rd

Subjects at risk321

325

279

249

232

192

195

158

157

123

128

89

85

48

42

21

12

7

1

30% RELATIVE RISK REDUCTIONHR 0.70; 95% CI (0.57, 0.85) P=0.0004* (Co-primary endpoint)

EMPLICITI + Rd (n=321)Rd (n=325)

68%

57%

27%

1- YEARPFS RATE

41%2- YEAR

PFS RATE

Prob

abili

ty P

rogr

essi

on-F

ree

(%)

Progression-Free Survival (Months)0 40363228242016124 8

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.

* 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.

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

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

Visit EmplicitiRx.com

EMPLICITI and the related logo are trademarks of Bristol-Myers Squibb Company. © 2015 Bristol-Myers Squibb Company. All rights reserved. 689US1500492-07-01 12/15

NEW

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EMPLICITI™ (elotuzumab) for injection, for intravenous useBrief Summary of Prescribing Information. For complete prescribing information consult official package insert.INDICATIONS AND USAGEEMPLICITI (elotuzumab) is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.

CONTRAINDICATIONSThere are no contraindications to EMPLICITI. Because EMPLICITI is indicated for use in combination with lenalidomide and dexamethasone, healthcare providers should consult the prescribing information of these products for a complete description of contraindications before starting therapy.

WARNINGS AND PRECAUTIONSInfusion ReactionsEMPLICITI can cause infusion reactions. Infusion reactions were reported in approximately 10% of patients treated with EMPLICITI with lenalidomide and dexamethasone in the randomized trial in multiple myeloma. All reports of infusion reaction were Grade 3 or lower. Grade 3 infusion reactions occurred in 1% of patients. The most common symptoms of an infusion reaction included 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.Administer premedication consisting of dexamethasone, antihistamines (H1 and H2 blockers) and acetaminophen prior to EMPLICITI infusion [see Dosage and Administration (2.2) in full Prescribing Information].Interrupt EMPLICITI infusion for Grade 2 or higher infusion reactions and institute appropriate medical management [see Dosage and Administration (2.3) in full Prescribing Information].InfectionsIn a clinical trial of patients with multiple myeloma (N=635), infections were reported in 81.4% of patients in the EMPLICITI combined with lenalidomide and dexamethasone (E-Ld) arm and 74.4% in lenalidomide and dexamethasone (Ld). 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-treated and 4.1% of Ld-treated patients. Fatal infections were reported in 2.5% and 2.2% of E-Ld- and Ld-treated patients.Opportunistic infections were reported in 22% of patients in the E-Ld arm and 12.9% of patients in the Ld arm. Fungal infections occurred in 9.7% of patients in the E-Ld arm and 5.4% of patients in the Ld arm. Herpes zoster was reported in 13.5% of patients treated with E-Ld and 6.9% of patients treated with Ld. Monitor patients for development of infections and treat promptly.

Second Primary MalignanciesIn a clinical trial of patients with multiple myeloma (N=635), invasive second 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 were the same between E-Ld and Ld treatment arms (1.6%). Solid tumors were reported in 3.5% and 2.2% of E-Ld- and Ld-treated patients, respectively. Skin cancer was reported in 4.4% and 2.8% of patients treated with E-Ld and Ld, respectively. Monitor patients for the development of second primary malignancies.

HepatotoxicityElevations in liver enzymes (aspartate transaminase/alanine transaminase [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 reported in 2.5% and 0.6% of E-Ld- and Ld-treated patients in a clinical trial of patients with multiple myeloma (N=635). Two patients experiencing hepatotoxicity were not able to continue 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 higher elevation of liver enzymes. After return to baseline values, continuation of treatment may be considered.

Interference with Determination of Complete ResponseEMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPEP) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein [see Drug Interactions]. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.

ADVERSE REACTIONSThe following adverse reactions are described in detail in other sections of the label:• Infusion reaction [see Warnings and Precautions].• Infections [see Warnings and Precautions].

• Second Primary Malignancies [see Warnings and Precautions].• Hepatotoxicity [see Warnings and Precautions].• Interference with Determination of Complete Response [see Warnings and

Precautions].Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse 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 observed in practice.The safety data described in this section are based on a randomized, open-label clinical trial in patients with previously treated multiple myeloma. In this study, EMPLICITI (elotuzumab) 10 mg/kg was administered with lenalidomide and dexamethasone [see Clinical Studies (14) in full Prescribing Information]. For adverse reaction evaluation, EMPLICITI combined with lenalidomide and dexamethasone was compared with lenalidomide and dexamethasone alone.The mean age of the population was 66 years and 57% of patients were 65 years of age or older. Sixty percent (60%) of the population were male, 84% were white, 10% were Asian, and 4% were black. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 47%, 1 in 44%, and 2 in 9% of patients.These data reflect exposure of 318 patients to EMPLICITI and 317 to control with a median number of cycles of 19 for EMPLICITI and 14 for control.Serious adverse reactions were reported in 65.4% of patients treated on the EMPLICITI arm and 56.5% for patients treated on the control arm. The most frequent serious adverse reactions in the EMPLICITI arm compared to the control arm were: pneumonia (15.4% vs. 11%), pyrexia (6.9% vs. 4.7%), respiratory tract infection (3.1% vs. 1.3%), anemia (2.8% vs. 1.9%), pulmonary embolism (3.1% vs. 2.5%), and acute renal failure (2.5% vs. 1.9%).The proportion of patients who discontinued any component of the treatment regimen due to adverse reactions as listed below was similar for both treatment arms; 6.0% for patients treated on the EMPLICITI arm and 6.3% for patients treated on the control.Adverse reactions occurring at a frequency of 10% or higher in the EMPLICITI arm and 5% or higher than the lenalidomide and dexamethasone arm for the randomized trial in multiple myeloma are presented in Table 1.

Table 1: Adverse Reactions with a 10% or Higher Incidence for EMPLICITI-Treated Patients and a 5% or Higher Incidence than Lenalidomide and Dexamethasone-Treated Patients [All Grades]

EMPLICITI + Lenalidomide and Dexamethasone

N=318

Lenalidomide andDexamethasone

N=317

Primary Term All Grades Grade 3/4 All Grades Grade 3/4

Fatigue* 61.6 12.6 51.7 11.7Diarrhea 46.9 5.0 36.0 4.1Pyrexia 37.4 2.5 24.6 2.8Constipation 35.5 1.3 27.1 0.3Cough† 34.3 0.3 18.9 0Peripheral Neuropathy‡ 26.7 3.8 20.8 2.2Nasopharyngitis 24.5 0 19.2 0Upper Respiratory Tract Infection 22.6 0.6 17.4 1.3Decreased Appetite 20.8 1.6 12.6 1.3Pneumonia§ 20.1 14.2 14.2 9.5Pain in Extremities 16.4 0.9 10.1 0.3Headache 15.4 0.3 7.6 0.3Vomiting 14.5 0.3 8.8 0.9Weight Decreased 13.8 1.3 6.0 0Lymphopenia 13.2 8.8 6.9 3.2Cataracts 11.9 6.3 6.3 2.8Oropharyngeal Pain 10.1 0 4.4 0

* The term fatigue is a grouping of the following terms: fatigue and asthenia.† The term cough is a grouping of the following terms: cough, productive cough, and upper

airway cough.‡ The term peripheral neuropathy is a grouping of the following terms: peripheral

neuropathy, axonal neuropathy, peripheral motor neuropathy, peripheral sensory neuropathy, and polyneuropathy.

§ The term pneumonia is a grouping of the following terms: pneumonia, atypical pneumonia, bronchopneumonia, lobar pneumonia, bacterial pneumonia, fungal pneumonia, pneumonia influenza, and pneumococcal pneumonia.

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Other clinically important adverse reactions reported in patients treated with EMPLICITI (elotuzumab) that did not meet the criteria for inclusion in Table 1 but occurred at a frequency of 5% or greater in the EMPLICITI group and at a frequency at least twice the control rate for the randomized trial in multiple myeloma are listed below:General disorders and administration site conditions: chest pain Immune system disorders: hypersensitivity Nervous system disorders: hypoesthesia Psychiatric disorders: mood altered Skin and subcutaneous tissue disorders: night sweats

Laboratory abnormalities worsening from baseline and occurring at a frequency of 10% or higher in the EMPLICITI group and 5% or higher than the lenalidomide and dexamethasone group (criteria met for all Grades or Grade 3/4) for the randomized trial in multiple myeloma are presented in Table 2.

Table 2: Laboratory Abnormalities Worsening from Baseline and with a 10% or Higher Incidence for EMPLICITI-Treated Patients and a 5% Higher Incidence than Lenalidomide and Dexamethasone-Treated Patients [Criteria met for All Grades or Grade 3/4]

EMPLICITI + Lenalidomide and Dexamethasone

N=318

Lenalidomide and Dexamethasone

N=317

Laboratory Parameter All Grades Grade 3/4 All Grades Grade 3/4

Hematology

Lymphopenia 99.4 76.7 98.4 48.7

Leukopenia 90.6 32.4 88.3 25.6

Thrombocytopenia 83.6 19.2 77.8 20.3

Liver and Renal Function Tests

Hypoalbuminemia 73.3 3.9 65.6 2.3

Elevated Alkaline Phosphatase 38.7 1.3 29.8 0

Chemistry

Hyperglycemia 89.3 17.0 85.4 10.2

Hypocalcemia 78.0 11.3 76.7 4.7

Low Bicarbonate 62.9 0.4 45.1 0

Hyperkalemia 32.1 6.6 22.2 1.6

Vital sign abnormalities were assessed by treatment arm for the randomized trial in multiple myeloma and are presented in Table 3. Percentages are based on patients who had at least one on-treatment vital sign abnormality any time during the course of therapy.

Table 3: Vital Sign Abnormalities

EMPLICITI + Lenalidomide and Dexamethasone

N=318

Lenalidomide and Dexamethasone

N=317

Vital Sign Parameter % %

Systolic Blood Pressure ≥160 mmHg 33.3 20.9

Diastolic Blood Pressure ≥100 mmHg 17.3 11.7

Systolic Blood Pressure <90 mmHg 28.9 8.2

Heart Rate ≥100 bpm 47.8 29.7

Heart Rate <60 bpm 66 31.3

ImmunogenicityAs with all therapeutic proteins, there is a potential for immunogenicity to EMPLICITI.Of 390 patients across four clinical studies who were treated with EMPLICITI and evaluable for the presence of anti-product antibodies, 72 patients (18.5%) tested positive for treatment-emergent anti-product antibodies by an electrochemiluminescent (ECL) assay. In 63 (88%) of these 72 patients, anti-product antibodies occurred within the first 2 months of the initiation of EMPLICITI treatment. Anti-product antibodies resolved by 2 to 4 months in 49 (78%) of these 63 patients. Neutralizing antibodies were detected in 19 of 299 patients in the

randomized trial in multiple myeloma. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to EMPLICITI (elotuzumab) with the incidences of antibodies to other products may be misleading.

DRUG INTERACTIONS

Drug InteractionsNo formal drug-drug interaction studies have been conducted with EMPLICITI. However, EMPLICITI is used in combination with lenalidomide and dexamethasone. Refer to the prescribing information for those products for important drug-drug interactions.

Laboratory Test InterferenceEMPLICITI may be detected in the SPEP and serum immunofixation assays of myeloma patients and could interfere with correct response classification. A small peak in the early gamma region on SPEP that is IgGƙ on serum immunofixation may potentially be attributed to EMPLICITI, particularly in patients whose endogenous myeloma protein is IgA, IgM, IgD, or lambda light chain restricted. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein [see Warnings and Precautions].

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk SummaryThere are no studies with EMPLICITI with pregnant women to inform any drug associated risks. Animal reproduction studies have not been conducted with elotuzumab.EMPLICITI is administered in combination with lenalidomide and dexamethasone.Lenalidomide can cause embryo-fetal harm and is contraindicated for use in pregnancy. Refer to the lenalidomide and dexamethasone prescribing information for additional information. Lenalidomide is only available through a REMS program.The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

Lactation

Risk SummaryThere is no information on the presence of EMPLICITI in human milk, the 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 elotuzumab administered with lenalidomide/dexamethasone, breastfeeding is not recommended. Refer to the lenalidomide and dexamethasone prescribing information for additional information.

Females and Males of Reproductive Potential

Pregnancy Testing Refer to the lenalidomide labeling for pregnancy testing requirements prior to initiating treatment in females of reproductive potential.When EMPLICITI is used with lenalidomide, there is a risk of fetal harm, including severe life-threatening human birth defects associated with lenalidomide, and the need to follow requirements regarding pregnancy avoidance, including testing.

ContraceptionRefer to the lenalidomide labeling for contraception requirements prior to initiating treatment in females of reproductive potential and males.Lenalidomide is present in the blood and semen of patients receiving the drug. 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.

Pediatric UseSafety and effectiveness have not been established in pediatric patients.

Geriatric UseOf the 646 patients across treatment groups in the randomized trial in multiple myeloma, 57% were 65 years of age or older; the number of patients 65 years or older was similar between treatment groups. No overall differences in efficacy or safety were observed between patients 65 years or older and younger patients (less than 65 years of age).

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6

OVERDOSAGEThe dose of EMPLICITI (elotuzumab) at which severe toxicity occurs is not known. EMPLICITI does not appear to be removed by dialysis as determined in a study of patients with renal impairment.In case of overdosage, monitor patients closely for signs or symptoms of adverse reactions and institute appropriate symptomatic treatment.

PATIENT COUNSELING INFORMATIONAdvise the patient to read the FDA-approved patient labeling (Patient Information).Infusion Reactions• EMPLICITI may cause infusion reactions. Advise patients to contact their

healthcare provider if they experience signs and symptoms of infusion reactions, including fever, chills, rash, or breathing problems within 24 hours 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 and Administration (2.2) in full Prescribing Information]:• Dexamethasone orally as prescribed• H1 blocker: diphenhydramine or equivalent (if oral)• H2 blocker: ranitidine or equivalent (if oral)• Acetaminophen (650-1000 mg orally)

Pregnancy• Advise patients that lenalidomide has the potential to cause fetal harm

and has specific requirements regarding contraception, pregnancy testing, blood and sperm donation, and transmission in sperm. Lenalidomide is only available through a REMS program [see Use in Specific Populations].

Infections

• Inform patients of the risk of developing infections during treatment with EMPLICITI (elotuzumab), and to report any symptoms of infection [see Warnings and Precautions].

Second Primary Malignancies

• Inform patients of the risk of developing SPM during treatment with EMPLICITI [see Warnings and Precautions].

Hepatotoxicity

• Inform patients of the risk of hepatotoxicity during treatment with EMPLICITI and to report any signs and symptoms associated with this event to their healthcare provider for evaluation [see Warnings and Precautions].

Manufactured by: Bristol-Myers Squibb Company Princeton, NJ 08543 USA

U.S. License No. 1713

1343639 Issued November 2015

689US1502988-03-01

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ASHBy the Numbers

The Need is in the Numbers Sickle Cell Disease (SCD)1: • Affects 70,000 to 100,000 Ameri-

cans

• 3 million Americans have sickle cell trait

• During 2005, medical expenditures for children with SCD averaged $11,702 for children with Medicaid coverage and $14,772 for children with employer-sponsored insurance

Leukemia2: • 54,000+ estimated new in cases in

2015

• 300,000 people living with leuke-mia in the U.S.

• 24,000 deaths in 2015

• 58% of people survive 5 years

Blood Clots (deep vein thrombosis and pulmo-nary embolism)3:• 600,000 Americans affected each

year; causes more deaths than breast cancer and AIDS combined

• #1 cause of maternal death in the U.S.

• 33% of patients will have a recur-rence in 10 years

• $10 billion in related medical costs in the U.S. each year

Myeloma2:• 100,000 new cases each year

• 0.7% lifetime risk of being diag-nosed with multiple myeloma, based on 2010-2012 data

• 89,658 people living with myeloma in the U.S., in 2012

ASH 2015 at a Glance

57th

annual session

20,000 attendees

3,000 presented abstracts

70th

birthday of Blood1. Sickle Cell Disease Association of America. sicklecelldisease.org. 2015. 2. National Cancer Institute. seer.cancer.gov/statfacts. 2015. 3. Clot Connect. Clotconnect.org. March 29, 2014.

Make the Change You Want To See Modifying Cells and Receptors for Better Outcomes

One of the key problems with choosing a care pathway is that it is impossible to predict to what treatments people will respond—a

single disorder or ailment may have a dozen different approved therapies that still, ultimately, act as blanket therapies. Creating targeted therapies that address the specific issue in each specific patient is ideal.

Scores of sessions presented findings on ways to change or modify genetic expression to help cells do what they do best—attack malignancies, for ex-ample—or inhibit the body from causing itself harm, such as promoting malignant cell growth. The use of chimeric antigen receptor (CAR) T cells was of particu-lar interest in many of the trials.

James N. Kochenderfer, MD, and colleagues presented their efforts to improve the treatment of B-cell malignancies after allogeneic transplantation by infusing allogeneic T cells that were genetically modified to express an anti-CD19 CAR. The relapse of malignancy is the key factor in the rate of death in patients who have undergone allogeneic stem cell transplantation because B-cell malignancies persist and are, consequently, treated with unmanipulated donor lymphocyte infusions; however, these donor infusions may have inconsistent efficacy and can initiate morbid-ity and mortality from graft-versus-host disease. In their study, 20 patients with persistent malignancies (even after their allogenic transplantation) were given modified CAR T cells that were culled from the original transplant donor. Two weeks after the infusion of the modified cells, the participants showed a marked posi-tive response. “Allogeneic anti-CD19 CAR T cells have significant anti-malignancy activity when administered without prior chemotherapy,” said Dr. Kochender-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 seem to be particularly effective against ALL and CLL.”1

Danhof and colleagues had similar success with CAR T cells for the treatment of multiple myeloma. 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

ASH 2015

7

ASH will “continue to work with our colleagues in industry.”

—David A. Williams, MD

Getting It Right

Precision Medicine, New Therapies, and Industry Evolutions

One of the questions in focus at the 57th American Hematology Society (ASH) Annual Meeting & Exposition was how to get it right—how to create

the right care path for the right patient, how to choose and use new therapies, and how to best collaborate as an industry to optimize health care.

“The ASH meet-ing is internation-ally renowned not only for its diverse programming and high-caliber science, but also for its unique ability to foster collaboration among hematolo-gists worldwide,” said ASH President David A. Williams, MD, in his confer-ence welcoming. On working with managed care professionals, Dr. Williams said that ASH will “continue to work with our colleagues in industry to make sure that we help to find targets for new drugs and help industry develop new drugs that will help our patients—to play a role with our colleagues in industry, making sure our practitioners understand, as new drugs come on line, how these can be applied most effectively to our patients.”

The following pages feature conference highlights, from targeted therapies to newly approved drugs to negotiating changing industry policies—all geared toward creating the best possible health care system for patients. ●

David A. Williams, MD

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Population UpdatesWhile blood may be one of the most common shared traits we have, there is an ever-evolving body of knowl-edge showing that individual demographics require targeted and, in many cases, improved care. ASH 2015 was rich with research showing this to be true. Here are some of the findings.

Black pediatric patients with acute myeloid leukemia present with more acute illness at initial diagnosis, ac-counting for up to 63% of the relative excess induction mortality. Identifying factors impacting acuity of illness at presentation and associated with public insurance may help to identify opportunities for intervention and thus nar-row the current racial disparities in pediatric AML survival.  (Winestone et al. ABSTRACT #530.)

Older patients with acute myeloid leukemia (AML) have high health care cost utilization that reflects the bur-den of the disease, even with a decision to not receive chemotherapy. Despite this population’s poor prognosis, palliative care and hospice services are rarely utilized. Future work should study novel health care delivery models designed to meet the needs of this population. (El-Jawahri et al. ABSTRACT #2126.)

Women with sickle cell disease (SCD) have unmet con-traceptive needs, having limited knowledge about their obstetric risks, and this knowledge appears to come from their lived experience and provider counseling. (Whaley et al. ABSTRACT #3263.)

Older adults with newly diagnosed multiple myeloma (25% of study patients) commonly experience falls. Falls are associated with more limited activity, depression, and congestive heart failure. Prospective studies are needed to determine factors predictive of falls in order to target interventions to those at high fall-risk and to prevent falls. (Wildes et al. ABSTRACT #4485.)

jill m. johnson, mdGuiding Hematologic Care with Genetic Testing

“We have been doing, fundamentally, ge-netic 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 conducted by Rick McGuire.

an end—such as targeting tumor cells. Investigators questioned what effect it may have on myeloma cells in engineering a T cell specifically for the target of another drug—in this case, the elotuzumab target SLAMF7 (CS1, CD319).

 “SLAMF7 is uniformly and highly expressed in multiple myeloma (MM) where it promotes adhesion and survival of malignant plasma cells (mPCs) in the bone marrow niche,” presented Sophia Danhof, MD, study presenter. Elotuzumab, an anti-SLAMF7 monoclonal antibody (mAb), when used, has shown a reversible lymphodepletion and conferred potent anti-MM efficacy in combination therapy. Research-ers sought to evaluate whether SLAMF7-directed CAR engineered T cells could be generated from previously treated MM patients, and to gauge the potency of the patient-generated T cells against mPCs. Their trial sought to generate SLAMF7 cells from both MM patients and healthy donors. They were able to do so from both, but were surprised to find that proportion of SLAMF7+ cells was significantly higher in MM pa-tients compared to healthy participants. What’s more, despite a high level of SLAMF7 expression on the study population, T cells that expressed the SLAMF7-CAR could be readily generated in all MM patients and extended to therapeutically relevant doses in a single expansion cycle following enrichment.2 ●

1. ABSTRACT #99. 2. ABSTRACT #115.

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Clinical Applications of Newly Approved DrugsAn Interview with Mikkael A. Sekeres, MD, MS

In this interview, Rick McGuire, Executive Editor for American Medical Communications, speaks with Mikkael A. Sekeres, MD, MS, of the Cleveland Clinic, about three

newly approved drugs: idarucizumab, for the reversal of novel oral anticoagulant (NOAC); blinatumomab, for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R ALL); and panobinostat, for the treatment of patients with multiple myeloma. rick mcguire: What do we need to know about idarucizumab? mikkael a. sekeres, md: This is an interesting drug and an interesting indication. Dabigatran is an agent, of course, that is used as an anticoagulant in patients who have atrial fibrillation, or in patients who have had a blood clot. Sometimes, these patients are on an anticoagulant when something terrible happens. In Cleveland, OH, they might be walking out on the sidewalk, slip on some ice, fall and hit their head, and develop an intracranial hemorrhage. They come to the emergency room and, up until now, there hasn’t been an effective agent to reverse that bleeding. We have one now in the form of idarucizumab, and it’s a drug that works for urgent situations.

But one concern is that this is an expensive drug, and we must first define what constitutes an emergency or urgent indication for it. And then where are you going to stock it? A large institution like Cleveland Clinic, sure, we are going to see these patients and we are going to stock the agent in our main hospital. But if you’re at a smaller institution, is it worth keeping this drug on the shelf when, eventually, it may expire and you’ll have to absorb the cost of that drug?

The second new agent, blinatumomab, is for the treatment for Philadelphia chromosome-negative relapsed or refractory precursor B-cell acute lymphoblastic leukemia. Impressions of this drug? We’ve actually used this agent a lot. Blinatumomab is a monoclonal antibody that works in patients who do not have any drugs approved for their diagnosis—acute lymphoblastic leukemia. We can cure about 40% of these patients, but that means we can’t for about 60%; all of those folks are destined to either relapse or die. For these patients, we finally have a drug that’s approved that really does work, and works for a durable period of time.

As with idarucizumab, one of the challenges with blinatumomab is that it’s very expensive, and it requires an inpatient stay, followed by a transition to outpatient care. This has logistically been very challenging for a lot of cancer

centers to institute. And as was the case with idarucizumab, blinatumomab was approved based on an accelerated approval pathway, which means that there is a phase 3 study with a more clinically meaningful endpoint—so instead of just knowing the response rate and durable response survival, we are waiting for the results of that phase 3 trial to come out.

The third agent in your panel, panobinostat, was approved earlier this year for the treatment of patients with multiple myeloma. There have been a variety of new agents approved for multiple myeloma. Where does this one fit in?Panobinostat is approved as part of combination therapy based on interim markers of clinically meaningful benefits. So we are waiting for a phase 3 study with a more durable endpoint to emerge. Sagar Lonial, MD, who presented the data on this agent, sees a role for using this drug in combination with bortezomib and dexamethasone in patients who have failed a former immunologitory drug. So he uses it in patients whom he thinks have a more proliferative multiple myeloma.

Even with the cost of these new drugs, which can complicate things, I am hopeful. ●

FDA-Approved Hematology Therapies in 2015*

Parathyroid hormone: hormonal injection for the control of hypocalcemia in patients with hypoparathyroidism.

Panobinostat: HDAC inhibitor for the treat-ment of patients with multiple myeloma.

Recombinant Factor VIII: intravenous agent for the treatment of prophylaxis and treatment of hemophilia A.

Patiromer: polymer medicine that binds po-tassium for the treatment of hyperkalemia.

Idarucizumab: urgent-care agent for the reversal of the anticoagulant effects of dabigatran.

Ixazomib: oral proteasome inhibitor treat-ment of multiple myeloma.

Elotuzumab: immunostimulatory anti-body for the treatment of multiple myeloma.

Daratumumab: monoclonal antibody for the treatment of multiple myeloma.

*In order of approval date. Does not reflect all 2015 approved hematology drugs. Source: fda.gov.

Mikkael A. Sekeres, MD, MS

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

Patients with relapsed/refrac-tory MM (RRMM) after one to three prior therapies can now be

treated with elotuzumab, an immunos-timulatory monoclonal antibody (mAb) that recognizes Signaling Lymphocytic Activation Molecule F7 (SLAMF7), a protein highly expressed by myeloma and natural killer cells.

Elotuzumab has a dual mechanism of action, directly activating natural killer cells and initiating antibody-dependent cell-mediated cytotoxicity targeted against myeloma cells, with negligible effect on normal tissues.

Meletios A. Dimopoulos, MD, and colleagues shared the updated safety and efficacy follow-up results of the ELOQUENT-2 trial, a phase 3, random-ized, open-label study of elotuzumab

in combination with lenalidomide and dexamethasone in patients with RRMM. Patients (median age 66 years; 20% ≥75 years old; median number of therapies 2; 35% refractory to their last therapy) with RRMM were randomized 1:1 to elotu-zumab with lenalidomide/dexamethasone (ELd) or lenalidomide/dexamethasone (Ld) alone in 28-day cycles until disease progression or unacceptable toxicity. The co-primary endpoints were progression-free survival (PFS) and overall response rate (ORR), while overall survival and health-related quality of life were also considered.

The 2-year PFS interim analysis of the trial revealed that ELd treatment resulted in a 30% reduction in the risk of disease progression or death com-pared with Ld alone (HR 0.70 [95% CI:

0.57, 0.85; p = 0.0004]). Moreover, ELd showed a 79% overall response rate ORR, compared with 66% in the Ld arm. The most common adverse reactions (≥20%) were fatigue, diarrhea, pyrexia, constipation, cough, peripheral neuropa-thy, nasopharyngitis, upper respiratory tract infection, decreased appetite, and pneumonia, occurring, statistically, more in the ELd arm.

“The addition of elotuzumab to Ld led to an effective and durable benefit, representing a novel approach to treat-ing MM,” said presenters. “The updated safety and tolerability data reported were consistent with previous findings, confirming that there are minimal in-cremental toxicities associated with the addition of elotuzumab.” ●

ABSTRACT #653.

late-breaker

First Results from a Pilot Phase 2 Study in Children with Primary HLH

A novel targeted approach to the treatment of Hemo-phagocytic Lymphohistiocytosis (HLH) with an anti-interferon gamma (IFNγ) monoclonal antibody

(mAb), NI-0501, offers an innovative targeted and potentially less toxic approach to HLH management, according to the pilot phase 2 investigators. NI-0501 is a fully human, high affinity, anti-IFNγ mAb that binds to and neutralizes human IFNγ, of-fering a novel and targeted approach for the control of HLH.

Primary HLH (pHLH) is a rare immune regulatory disorder with complete mortality if untreated. The disorder is sustained by pathologic immune activation, initiating the development of fever, splenomegaly, cytopenias, and coagulopathy, which ulti-mately may cause multi-organ failure and death. The elevated production of IFNγ is thought to be key in the development of the disease, based on data from murine models of primary and secondary HLH (sHLH). Observational studies in patients with HLH, immune-chemotherapy, primarily etoposide-based regi-mens, is at present the only pharmacological approach able to control HLH and bring patients to curative allogeneic hemato-

poietic stem cell transplant (allo-HSCT). Drug-related toxicities contribute to the rate of death for those with HLH even with increasingly intensified treatment regimens.

A total of 13 HLH patients (aged 2.5-13 years) were en-rolled. Twelve patients received NI-0501 as a second line treat-ment after having received conventional therapy and either reactivating, obtaining unsatisfactory response, or being intol-erant to therapy. One patient was treated with NI-0501 in first

NI-0501 is a safe and effective therapeutic option in patients with pHLH who have demonstrated unsatisfactory response, or are intolerant, to conventional therapy.

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

Patients undergoing oncology infu-sion therapy that occurs in physi-cian office (PO) settings instead of

hospital outpatient (HO) settings may see treatment benefits. The rising trend of community-clinic acquisitions by hos-pitals has led to an increase in therapies occurring in HO settings instead of a PO. Recent studies have suggested that differences between sites of care (SOC) can impact cancer treatment delivery and overall health care costs. Casebeer et al. investigated, in this study, differences in treatment patterns, cost, and quality of care among predominately Medicare, (85%) patients with NHL/CLL receiving infusion chemotherapy and/or rituximab in a HO versus PO setting.

Using Humana medical claims data, study investigators identified 1,859 patients (≥18 years) who had been given infusion therapy in 2008-12 with at least two claims with a diagnosis of NHL or CLL occurring 30 or more days apart.

SOC attribution (HO vs. PO) was based on where patients received ≥90% of their infusions. Health care costs were deter-mined by the sum of plan and patient costs for medical and pharmacy claims in the 6 months following the index date, and considered oncology costs, including supportive care.

The results found many differences between the infusion therapy duration and treatment between PO and HO set-tings. Those treated in HO settings had:

• A higher mean comorbidity index compared to PO patients,

• An increased use of rituximab monotherapy,

• An increased use of rituximab with chemotherapy,

• Higher health care costs ($60,536) compared to PO setting ($49,800),

• 24% higher total oncology-related health care costs ($58,033) com-pared with PO ($46,652).

However, among those receiving che-motherapy only, treatment duration was shorter in the HO setting with 78.5 days vs. the PO setting with 112 days. In the HO setting, there were fewer infusions for patients receiving chemotherapy and rituximab, and chemotherapy only. And there were no statistically significant dif-ferences in the quality of care indicators by SOC, including the use of infusions or hospitalizations within 30 days of death among Medicare patients.

 “As care shifts from the PO to HO set-ting,” said Adrianne W. Casebeer, MPP, MS, PhD, “future studies should assess the impact of SOC on the delivery of care and health care costs associated with cur-rent therapeutic options for NHL/CLL.” ●

ABSTRACT #3298.

line. Most study participants had severe HLH, in compromised general condition (two patients in ICU) and carrying significant toxicities from previous HLH treatments.

“Overall, NI-0501 treatment significantly improved parameters of HLH disease activity,” said Michael Jordan, MD, study presenter, “and nine of 13 patients achieved a satisfactory response. Seven patients have proceeded to allo-HSCT. Allo-HSCT is planned for two patients with good HLH control upon identification of an appropriate donor.”

NI-0501 was well tolerated and no safety concerns were noted, including infections caused by IFNγ neutralization or in those patients who had not previously received chemotherapy, myelotoxicity, or hemo-dynamic alterations.

“The results of this study show that NI-0501 is a safe and effec-tive therapeutic option in patients with pHLH who have demon-strated unsatisfactory response, or are intolerant, to conventional therapy. Furthermore, therapy with NI-0501 was not associated with any of the typical short- or long-term toxicities reported for etoposide-based regimens. Assessment of NI-0501 as first line treatment for pHLH is ongoing,” said Dr. Jordan. ●

LATE-BREAKING ABSTRACT #3.

griffin rodgers, mdOptimizing Therapy in Sickle Cell Disease

“This was the first disease to be under-stood at the molecular level—the first genetic disease... So not only do we know the protein abnormality, we also know this genetic underpinning, and we have ready access to the stem cells of these patients in the form of the bone marrow or the peripheral blood cells. So treating the upstream complications is an area of investigation.”

To see the full interview with Griffin Rodgers, MD, scan the QR code or visit hematologydailyreport.amcp.org. Interview conducted by Rick McGuire.

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

While most agree that measuring and optimizing the quality of medical care is vital, there has been controversy on the best way to do so.

Rick McGuire, Executive Editor for American Medical Communications, spoke with Lisa K. Hicks, MD, MSc, at St. Michael’s Hospital and Asst. Professor at the University of Toronto, about some of these current and future changes.

rick mcguire: To start, why focus on quality measures? lisa k. hicks, md, msc: Quality metrics are a core, foundational topic in quality-improvement sciences. I think it was W. Edwards Deming who said, “If you can’t measure it, you can’t manage it.” It is going to be increasingly important for our membership to have familiarity with quality metrics—specifically with pay-for-performance—especially those members from the United States, where the rate of change is extremely quick. It is no longer theoretical whether or not quality metrics are going to have an impact on their practices; it is very real.

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 do, and whether we are achieving the end points we want to

achieve, is a good thing. But how we get to the next milestone of using this quality improvement science, and using metrics to bring about positive change, is going to be the more difficult one.

The story isn’t finished, like so many things in hematology. One of the challenges in quality work is that it is very contextual, so it isn’t clear if what works in one specific context works in a different context.

What can be said to make people feel more comfortable with the direction of quality metrics? I would tell them to learn. It is important for individual physicians to find out about the changes that are occurring. Large practices or practice groups should have a point 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 improved care for our patients.

Are we going to get there easily? Probably not. We need physicians engaged, doing high-quality, innovative work, and pushing back. But not just physicians—other allied health workers and some of our non-physician academics need to be 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. ●

Lisa K. Hicks, MD, MSc

It is no longer theoretical whether or not quality metrics are going to have an impact on their practice; it is very real.

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Benefits of Patient-Reported Outcomes (PROs) for Clinicians, Patients and Industry

It is known that incorporating the patient perspective into health care is important—how to best do this was the focus of a special education program designated to explore how

PROs can be utilized into clinical care and research. Session moderator Ellen M. Werner, PhD, defined PRO as “the mea-surement of a patient’s perspective of a health condition and its treatment.” Examples would include “a patient’s report of func-tion, pain or other symptoms, satisfaction, and sleep quality.”

David Cella, PhD, shared how PRO measurements are developed, giving the Patient Reported Outcomes Measurement Information System (PROMIS), an NIH-funded program, as an example. PROMIS is a web-based portal wherein patients self-report their health status using various response templates. For physicians, the program creates a hub from which immedi-ate and updated PROs can be accessed to assist in diagnosis, therapy maintenance, etc. For researchers, PROMIS creates and validates instruments that measure the emotional state, function, and perceptions relevant to reported outcomes, even acting as primary or secondary endpoints in clinical and observational studies of the effectiveness of treatment. A special committee is being developed to work with industry members to explore how the PROMIS data can be used toward pharmaceutical, biotechnology, medical devices, and diagnostic organizations.

How to use PROs for drug development was also discussed by Virginia E. Kwitkowski, MS, NP. Specifically, Kwitkowski spoke of using PROs to develop drugs with the FDA in mind. The measures that the FDA currently uses take into account a patient’s survival, how a patient feels (in terms of health), and how a patient functions after using a therapy. This, she argues, is not enough, and a more modular approach is needed because therapies impact a patient in other “non-health” ways—qual-ity of life measurements, such as financial burden (the FDA

cannot consider “cost” when considering approval). Moreover, the data submitted to the FDA for approval currently focus on laboratory, radiography, and clinician-reported adverse events, despite the fact that some events can only be measured by patients. Patient-reported outcomes also do not affect product labeling, even though they clearly affect the patient. Kwitkows-ki argues that PROs have great potential to act as “guidance for the industry.” Many stakeholders are interested in under-standing the patient’s experience, which can only lead to better therapies that best serve those who use them.

PROs have a practical use in a physician’s daily practice, as well, argues Julie A. Panepinto, MD, MSPH. At their most basic level, PROs are already used with shared expres-sions between physicians and patients. Notes like, “Patient is doing fine” or “No concerns” are made in charts. This leaves a great amount of room for missing what is really going on with the patient, she argued. It is difficult to estimate patient function. An observational study revealed, for example, that health care providers did not identify 50% of symptoms in patients that were detected by a PRO measure; issues such as dyspnea, anorexia, pain, and insomnia were missed by more than 60% of health care providers studied. The severi-ty of a patient’s symptoms are often underestimated, as well. When compared, the clinician’s assessment of the patient and the patient’s own PRO revealed roughly a 50% disagree-ment rate. The benefits of using PROs in a clinical setting? They could alert physicians to patient problems, monitor a patient’s function over time, facilitate communication, and provide a patient with information on how they are doing compared to patients who are similar to them. What’s more, with the rise of electronic medical health records, digitized results from PROs can create a holistic picture that follows each patient as they utilize the health care system. ●

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