1. 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.

2. 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: ClinicalTrials.gov. NCT Stegelmann F, et al. ASH Abstract ClinicalTrials.gov. NCT
Slide credit: clinicaloptions.com

3. 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 Abstract 826.

4. 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 ( )
Median hemoglobin, g/dL (range)
8.8 ( )
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 Abstract 826.

5. 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 Abstract 826.

6. 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 Abstract 826. Reproduced with permission.

7. 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 Abstract 826.

8. 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 Abstract 826.

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