MPNSG-0212: Ruxolitinib + Pomalidomide Clinically Active and Well Tolerated in MF 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. MF, myelofibrosis. This program is supported by educational grants from Amgen, Celgene Corporation, Merck, Incyte, Seattle Genetics, and Takeda Oncology.

MPNSG-0212: Background Ruxolitinib treats splenomegaly and constitutional symptoms in MF Limited treatment options for cytopenia in MF Pomalidomide may improve anemia and thrombocytopenia in some MF pts[1] MPNSG-0109 trial reports superior efficacy of 2-mg dose of pomalidomide monotherapy vs 0.5 mg QD[2,3] MPNSG-0212 trial evaluates combination of ruxolitinib and pomalidomide to evaluate potential synergy in pts with MF[4] Current analysis reports on first 28 pts[3] MF, myelofibrosis. 1. Tefferi A, et al. J Clin Oncol. 2009;27:4563-4569. 2. ClinicalTrials.gov. NCT00949364. 3. Stegelmann F, et al. ASH 2015. Abstract 826. 4. ClinicalTrials.gov. NCT01644110. Slide credit: clinicaloptions.com

MPNSG-0212: Study Design Open-label, single-arm, multicenter phase Ib/II trial 2-stage design: extend recruitment if response achieved in ≥ 12/37 pts Primary endpoint: RR after 12 cycles per IWG-MRT criteria, transfusion independence Secondary endpoints: PFS, DOR, OS, QoL, and safety Adults with untreated or pretreated primary or secondary MF with anemia, platelets > 100/nL (N = 28) Pomalidomide 0.5 mg PO QD + Ruxolitinib 10 mg* PO BID 28-day cycles 12 cycles planned with extension considered; safety, efficacy evaluated every 28 days *Initial dose; modifications allowed to optimize efficacy, manage myelosuppression DOR, duration of response; MF, myelofibrosis; QoL, quality of life; RR, response rate. Slide credit: clinicaloptions.com Stegelmann F, et al. ASH 2015. Abstract 826.

MPNSG-0212: Baseline Characteristics Ruxolitinib + Pomalidomide (N = 28) Median age, yrs (range) 74 (49-81) Pretreated, n (%) 13 (46) Median spleen size by ultrasound, cm (range) 17.5 (12.6-28) Median hemoglobin, g/dL (range) 8.8 (6.8-11.7) RBC transfusion dependent, n (%) 8 (29) Mutation, n (%) JAK2 V617F MPL W515L CALR 19 (68) 3 (11) 6 (21) DIPSS risk, n (%) Low Intermediate-I Intermediate-II High 1 (4) 2 (7) 20 (71) 5 (18) DIPSS, Dynamic International Prognostic Scoring System; RBC, red blood cell. Slide credit: clinicaloptions.com Stegelmann F, et al. ASH 2015. Abstract 826.

MPNSG-0212: Efficacy At analysis, 16/28 pts (57%) still on treatment 10 (36%) achieved stable disease; median cycles: 9 (2-17) 6 (21%) achieved clinical improvement; median cycles: 12.5 (9-18) Spleen, neutrophil count, hemoglobin, or transfusion independence Of evaluable pts, 14% showed reduction of splenomegaly, 7% cytopenia improvement Median time to response: 5 cycles (2-14) Mean hemoglobin increased from 8.9 g/dL at baseline (N = 28) to 10.2 g/dL at cycle 12 (n = 5) Largest increases post cycle 9 for pts still on treatment Slide credit: clinicaloptions.com Stegelmann F, et al. ASH 2015. Abstract 826.

MPNSG-0212: Mean Hemoglobin Over Time 10.2 10 9.5 9 8.5 8 8.9 Hemoglobin, g/dL [cycle] 1 2 3 4 5 6 7 8 9 10 11 12 n = 28 n = 25 n = 20 n = 13 n = 5 Mean hemoglobin increased from 8.9 g/dL at baseline to 10.2 g/dL at cycle 12 Largest increases post cycle 9 for pts still on treatment Slide credit: clinicaloptions.com Stegelmann F, et al. ASH 2015. Abstract 826. Reproduced with permission.

Ruxolitinib + Pomalidomide MPNSG-0212: Safety Total number of events: 312 13 serious AEs, 3 related to treatment Neuropathy, anemia, and increases in liver enzymes 2 deaths, unknown if related to treatment Cardiac decompensation, septic shock AE Occurring in ≥ 3 Pts, n Ruxolitinib + Pomalidomide (N = 28) Grade 1/2 Grade 3/4 Anemia 3 10 Fatigue Dyspnea 8 Abdominal pain 5 2 Musculoskeletal pain 1 Dizziness Infection Hyperuricemia Renal (peripheral edema) AE, adverse event. Slide credit: clinicaloptions.com Stegelmann F, et al. ASH 2015. Abstract 826.

MPNSG-0212: Conclusions Combination of ruxolitinib and pomalidomide relatively well tolerated and clinically active in a pretreated and high-risk MF pt group Investigators conclude that combination therapy feasible Serious events likely related to drug were manageable 36% of pts had stable disease, some continuing treatment beyond 12 cycles Hematopoietic response seen later than spleen response Interim analysis planned after 37 pts; will consider higher pomalidomide dose to improve anemia response MF, myelofibrosis. Slide credit: clinicaloptions.com Stegelmann F, et al. ASH 2015. Abstract 826.

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