Phase II Study of Low-Dose Pomalidomide in Patients with Myelofibrosis and Significant Anemia (hemoglobin <10g/dL)

Pomalidomide (POM) is a new investigational immunomodulatory drug (iMID) that has shown promise in the treatment of patients with myelofibrosis (MF) by improving their hemoglobin and eliminating a need for blood transfusions. This significant clinical activity was seen in up to 36% of patients (according to International Working Group for Myelofibrosis Research and Therapy response criteria) when POM was used at the low (0.5mg) continuous daily oral dose, with or without concomitant use of prednisone. Based on these results, Phase III blinded, placebo-controlled study is underway globally, for possible approval of POM, as a single agent, for MF patients with significant anemia and transfusion dependency. However, the response criteria utilized in the Phase III study is more robust and clinically meaningful transfusion dependency/independency criteria, so called “Gale criteria” (Gale et al. Leuk Res. 2011 Jan;35(1):8-11.). Patients are also assessed for an increase in hemoglobin of 2g/dL from baseline, for a duration of at least 8 weeks.

Our single-center Phase II open-label study examined the efficacy of a single agent, low dose (0.5mg/day) POM in improving hemoglobin and reducing/eliminating transfusion requirements (based on Gale criteria) specifically in patients with MF and significant anemia (hemoglobin <10g/dL). The study is ongoing.

28 patients, 14 male and 14 female, were enrolled in the study: 10 (35%) had post essential thrombocythemia MF, 17 (60%) had primary MF and 1 (3%) post polycythemia vera MF. Median age was 65 years (range 38–84) and 12 (42%) were previously treated (none with thalidomide or lenalidomide). Twelve (42%) had splenomegaly; 2 had prior splenectomy. Eighteen had diploid karyotype and 17 had JAK2V617F mutation. All patients had to have hemoglobin <10g/dL; patients with higher hemoglobin that were transfusion dependent were allowed to enroll if it was a result of a blood transfusion given just before enrollment. Median hemoglobin was 9.2g/dL (range 7.3–11.1), WBC 5.2×10^9/L (2–21.7), and platelets 224×10^9/L (53–1478). 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. Eight patients were “transfusion dependent” by Gale criteria.

After median follow up of more than a year, 11 (40%) patients were still on therapy. Median number of cycles given to patients was 11. Twelve patients were taken off the study for no response, 2 transformed to acute leukemia, 3 died from unrelated causes. The therapy was well tolerated; there were no instances of Grade 3/4 neutropenia or thrombocytopenia or non-hematologic toxicity. By Gale criteria 2 of 8 transfusion dependent patients achieved transfusion independence; both were JAK2 mutation negative and did not have splenomegaly. No patient experienced sustained increase in hemoglobin of 2g/dL from baseline. Updated results will be presented at the meeting.

POM administered to patients with MF with significant anemia at an oral dose of 0.5 milligrams daily has a good safety profile and modest clinical activity.

Verstovsek:Celgene: Research Funding.