Phase II Study: Pembrolizumab + Pomalidomide/Dexamethasone for Patients With R/R MM New Findings in Hematology: Independent Conference Coverage* of ASH 2015, December 5-8, 2015, Orlando, Florida *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. This program is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, Seattle Genetics, and Takeda Oncology.

Pembrolizumab + Pomalidomide/ Dexamethasone in R/R MM: Background  PD-L1 overexpression associated with invasiveness and tumor-mediated immune suppression in MM  Pembrolizumab: highly selective anti–PD-1 mAb –Approved in advanced NSCLC and melanoma –May activate myeloma-specific cytotoxic T cells that can be further enhanced by pomalidomide  Study evaluated safety and efficacy of pembrolizumab with pomalidomide + dexamethasone in relapsed/refractory MM Badros AZ, et al. ASH Abstract 506. Slide credit: clinicaloptions.comclinicaloptions.com

Pembrolizumab 200 mg IV D1,14* Pomalidomide 4 mg PO D1-21 Dexamethasone 40 mg † PO D1,7,14,21 28-day cycles until PD Phase II Study: Pembrolizumab + Pomalidomide/Dexamethasone in R/R MM  Primary endpoint: safety  Secondary endpoints: ORR, time to disease progression  Exploratory correlative studies: association of PD-1/PD-L1 expression in bone marrow with response, identification of functional myeloma-specific T-cell subsets Pts with R/R MM with ≥ 2 prior therapies including PI and IMiD; excluded pts with active or severe autoimmune disease (N = 33) After 24 mos responding pts can continue pomalidomide/ dexamethasone until PD Badros AZ, et al. ASH Abstract 506. *First 6 pts treated on D1 only. † 20 mg for pts older than 70 yrs of age. Slide credit: clinicaloptions.comclinicaloptions.com

Pembrolizumab + Pom/Dex in R/R MM: Baseline Characteristics Badros AZ, et al. ASH Abstract 506. CharacteristicPembrolizumab + Pom/Dex (N = 33) Median age, yrs (range)65 (42-81) Male, %73 High-risk cytogenetics,* %42 Median LDH, IU/L (range)415 ( ) Median time since diagnosis, yrs (range)3.7 ( ) Prior therapies, median (range)  ASCT, % 3 (2-5) 67 Refractory to, %  Any PI Bortezomib Carfilzomib Oprozomib  Lenalidomide  PI + IMiD Slide credit: clinicaloptions.comclinicaloptions.com *Includes pts with del(17p), t(4;14), t(14;16).

Pembrolizumab + Pom/Dex in R/R MM: Safety and Tolerability  Predictable and manageable safety profile (N = 33) –Most common grade ≥ 3 events: anemia, pneumonia, neutropenia, thrombocytopenia, hyperglycemia, dyspnea –Immune-related AEs included: pneumonitis, hypothyroidism, and hepatitis –1 grade 5 infection event  High infection rate; all pts given antibiotic prophylaxis  Dose modifications/reductions –Pembrolizumab modification during pneumonitis steroid treatment –5 pts required pomalidomide dose reduction due to AE  11/33 pts discontinued treatment, 9 due to progression Badros AZ, et al. ASH Abstract 506. Slide credit: clinicaloptions.comclinicaloptions.com

Pembrolizumab + Pomalidomide/ Dexamethasone in R/R MM: Efficacy  M-protein or FLC reduction from baseline of up to 85%  Durable responses; median time to best response: 2 mos (range 1-9)  Median PFS, OS not reached with short 7.4-mo follow-up Outcome, % Evaluable Pts (N = 27) Double Refractory (n = 20) High-Risk Cytogenetics (n = 12) ORR  sCR  CR  VGPR  PR SD30 42 PD10158 Badros AZ, et al. ASH Abstract 506. Slide credit: clinicaloptions.comclinicaloptions.com

Pembrolizumab + Pomalidomide/ Dexamethasone in R/R MM: Conclusions  Pembrolizumab in combination with pomalidomide/ dexamethasone shows promising activity in heavily pretreated R/R MM –Early evidence of deep, durable responses  Combination has tolerable and manageable safety profile  Ongoing exploratory analyses: –To standardize and analyze PD-L1 expression on bone marrow samples to assess value as biomarker –To define functional myeloma-specific T-cell subsets Badros AZ, et al. ASH Abstract 506. Slide credit: clinicaloptions.comclinicaloptions.com

Go Online for More CCO Coverage of ASH 2015! Short slideset summaries of all the key data Additional CME-certified analyses with expert faculty commentary on all the key studies in:  Acute leukemias/chronic leukemias  Myeloma/plasma cell disorders  Lymphomas  MDS and myeloproliferative neoplasms clinicaloptions.com/oncology