A Phase II Study of Low-Dose Pomalidomide (0.5mg/day) and Prednisone Combination Therapy in Patients with Myelofibrosis and Significant Anemia

Pomalidomide (POM) is an investigational immunomodulatory drug (IMID) that has shown efficacy in preliminary studies, with or without prednisone, as therapy for myelofibrosis (MF) with anemia, by eliminating the need for red blood cell (RBC) transfusions. In our experience, however, single agent low dose POM (0.5 mg/d) has very modest efficacy in achieving RBC transfusion independence in MF patients (Shastri A et al Blood 2011; 118). To further understand and define its activity, we have undertaken a single center phase II open label study to assess the efficacy of low dose POM in combination with prednisone therapy. In a prior study this combination resulted in a 36% response rate according to International Working Group for Myelofibrosis Research and Therapy (IWG-MRT) response criteria (Tefferi A, et al. JCO 2009; 27:4563). In the current study, benefit was assessed by the RAND-Delphi consensus criteria, which has been suggested as a better tool to evaluate RBC transfusion dependence/independence in clinical trials (Gale RP et al. Leuk Res 2011; 35:8) than IWG-MRT criteria. Patients were also evaluated for an increase in hemoglobin of at least 2g/dL for duration of 8 weeks, without transfusion support.

21 patients, 14 male and 7 female, were enrolled in the study: 2 (10%) had post essential thrombocythemia MF, and 19 (90%) had primary MF. Median age was 69 years (range 48–85) and 15 (71%) were previously treated; 5 had been treated with other IMIDs previously. Four (19%) had splenomegaly; 1 had prior splenectomy. Seven (33%) had abnormal cytogenetics and 10 (48%) had JAK2V617F mutation. All patients had hemoglobin <10g/dL at study entry; patients with higher hemoglobin that were transfusion dependent were allowed to enroll if it was a result of a blood transfusion given just prior to enrollment. Median hemoglobin was 8.5 g/dL (range 7.3–11.1), WBC 4.7×10⁹/L (1–20.7), and platelets 155×10⁹/L (35–1191). The use of anagrelide during the study was allowed to control high platelets, if indicated; other concomitant therapies, including growth factors, were not allowed. Patients were administered POM 0.5mg continuously daily in 28-day cycles and prednisone was administered as 30mg daily for the first month, 15mg daily for second month, 15mg every other day for third month and then stopped. Thirteen (62%) patients were transfusion dependent by the RAND-Delphi consensus criteria.

After a median follow up of 7.8 months (3.3–11.9), 6 (28%) patients were still on the therapy. The median number of cycles administered to patients was 6 (2–12). Fourteen patients were taken off the study for lack of response (N=12) or for loss of a response (N=2). One patient was taken off due to the development of grade 3 pneumonitis. Three died from unrelated causes. Three patients were noted to have RBC transfusion response per RAND-Delphi criteria. One of the responders had JAK2V617F mutation. Median time to response was 52.7 days (48 – 55 days). No patient had an increase in hemoglobin of at least 2g/dL for at least 8 weeks. This is an ongoing trial and updated results along with complete toxicity profile will be presented at the meeting.

POM administered in combination with prednisone to patients with MF and significant anemia has modest efficacy, comparable to single agent POM. A Phase III blinded, placebo-controlled study is underway globally for MF patients with significant anemia and RBC transfusion dependency.

Verstovsek:Celgene: Research Funding.