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663 Pomalidomide Therapy in Anemic Patients with Myelofibrosis: Results from a Phase-2 Randomized Multicenter Study

Oral and Poster Abstracts
Oral Session: Myeloproliferative Disorders-Clinical Trials
Monday, December 8, 2008: 5:00 PM
Gateway Ballroom 104 - South (Moscone Center)

Ayalew Tefferi, MD1, Srdan Verstovsek, MD, PhD2, Giani Barosi3*, Francesco Passamonti, MD4*, Gail J. Roboz, MD5, Heinz Gisslinger6, Ronald Paquette, MD7, Francisco Cervantes, MD8, Candido E. Rivera, MD9, H. Joachim Deeg10, Juergen Thiele11*, Hans Michael Kvasnicka11*, James W. Vardiman, MD12, B. Nebiyou Bekele, PhD13*, Ruben A. Mesa, MD, FACP14, Robert P Gale15* and Hagop M Kantarjian16

1Hematology, Mayo Clinic, Rochester, MN
2Department of Leukemia, M.D. Anderson Cancer Center, Houston, TX
3IRCCS Policlinico San Matteo, Pavia, Italy
4Department of Hematology Oncology, University of Pavia & Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
5Medicine, Weill Cornell Medical College, New York, NY
6Department of Hematology and Blood Coagulation, Medical University of Vienna, Vienna, Austria
7Ronald Reagan UCLA Medical Center, Los Angeles, CA
8Dept. of Hematology, Hospital Clinic, Barcelona, Spain
9Mayo Clinic, Jacksonville, FL
10Fred Hutchinson Cancer Research Center, Seattle, WA
11Insitute of Pathology, University of Cologne, Cologne, Germany
12University of Chicago, Chicago, IL
13Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, TX
14Mayo Clinic, Rochester, MN
15Celgene Corporation, Summit, NJ
16The University of Texas M. D. Anderson Cancer Center, Houston, TX

BACKGROUND: Both thalidomide (Br J Haematol 2002;117:288) and lenalidomide (Blood 2006;108:1158) are effective for alleviating anemia in approximately 20% of patients with myelofibrosis (MF). However, the value of these drugs is undermined by their respective potential for peripheral neuropathy and severe myelosuppression. In the current study, we evaluated the safety and efficacy of the new immunomodulatory drug, pomalidomide (POM) in MF.

METHODS: This is a phase-2 randomized, multicenter, double-blind, active-control, parallel-group study to determine safety and select a “Best” dose of POM alone or combined with prednisone (PRED). Patients were equally randomized to 4 treatment groups: i) POM (2 mg/day) + placebo, ii) PRED (30 mg/day) + placebo, iii) POM (2 mg/day) + PRED (30 mg/day), and iv) POM (0.5 mg/day) + PRED (30 mg/day). POM therapy was given for up to twelve 28-day treatment cycles. PRED therapy was given in a tapering dose schedule during the first three of these 12 treatment cycles. Protocol eligibility criteria included absolute neutrophil count of 1 x 109/L, platelet count of 50 x 109/L and hemoglobin level of < 10 g/dL including red blood cell (RBC) transfusion requirement. Patients with prior thalidomide or lenalidomide therapy and/or venous thrombosis were excluded from study participation. Response was assessed by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria (Blood. 2006;108:1497) and by independent analysis of the component variables.

RESULTS: A total of 104 patients with MF were assessed for eligibility; 85 were randomized and 84 received the assigned therapy. Blinded data for the first 82 patients are presented here; median age was 67 years and MF subtype was PMF in 70% of the patients and post-PV/ET MF in 30%. All patients belonged to either intermediate or high risk disease category (Blood 1996;88:1013); 42 (51%) were RBC transfusion-dependent. Median duration of disease before randomization was 3 years (range 2-14). The number of patients assigned to each arm was relatively balanced: 21, 20, 19 and 22, respectively. After a median treatment duration of 3 months, 42 (51%) patients have discontinued protocol therapy because of lack of therapeutic effect (n=19), withdrawal of consent (n=11), adverse event (n=11) or death (n=2). Grade 3/4 adverse events (regardless of attribution) included anemia (10%), thrombocytopenia (9%), leukopenia (9%), fatigue (7%), dyspnea (5%), thrombosis (4%), diarrhea (4%) and hyperglycemia (4%). Combined response rate using IWG-MRT criteria was 25% (95% CI, 16-34%) and ranged between 11% and 42% among the four treatment arms.

CONCLUSION: Pomalidomide, with or without concomitant prednisone therapy, is well tolerated in patients with MF, especially from the standpoint of myelosuppression. Response rates are high. Additional, unblinded, information regarding response details, remission duration and laboratory correlative studies will be presented at the meeting.

Disclosures: Gale: Celgene: Employment.

*signifies non-member of ASH