Pomalidomide Therapy in Anemic Patients with Myelofibrosis: Results from a Phase-2 Randomized Multicenter Study
Authors: Tefferi Ayalew , Verstovsek Srdan , Barosi Giani , Passamonti Francesco , Roboz Gail J. , Gisslinger Heinz , Paquette Ronald , Cervantes Francisco , Rivera Candido E. , Deeg H. Joachim , Thiele Juergen , Kvasnicka Hans Michael , Vardiman James W. , Bekele B. Nebiyou , Mesa Ruben A. , Gale Robert P , Kantarjian Hagop M 
Published: October 2019

Abstract
BACKGROUND: Both thalidomide (Br J Haematol2002;117:288) and lenalidomide (Blood2006;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:
POM (2 mg/day) + placebo, PRED (30 mg/day) + placebo, POM (2 mg/day) + PRED (30 mg/day), and 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 × 109/L, platelet count of ≥ 50 × 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 (Blood1996;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.