A Phase-2 Trial of Low-Dose Pomalidomide In Myelofibrosis with Anemia

In a previous study, we reported safety and efficacy of low-dose (0.5 mg/d) pomalidomide and prednisone and pomalidomide alone (2 mg/d) for the treatment of anemia associated with myelofibrosis (J Clin Oncol 2009; 27: 4563). The current study examined the value of low dose pomalidomide alone (ClinicalTrials.gov No. NCT00669578).

Persons with primary (PMF) or post-polycythemia vera/essential thrombocythemia (post-PV/ET MF) myelofibrosis were studied. The main eligibility criterion was RBC-transfusion-dependence or hemoglobin <10 g/dL. Subjects failing lenalidomide or thalidomide were eligible whereas those with deep vein thrombosis or pulmonary-embolism <1 y pre-study entry were not. The primary endpoint was anemia response assessed by the International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria (Blood 2006; 108: 1497).

Pomalidomide (0.5 mg/d) was given to 58 subjects (median age 68 y; 44 males). 46 (79%) were RBC-transfusion-dependent and 42, JAK2V617F-positive. Baseline disease-stage at time of study-entry according to the Dynamic International Prognostic Scoring System (DIPSS; Blood 2010; 115: 1703) was high-risk in 16 (28%) and intermediate-2 risk in 42 (72%). Cytogenetic findings were favorable in 46, unfavorable in 9 and not evaluable in 3. 46 (79%) had PMF and the remainder post-PV/ET MF. 49 (84%) patients completed ≥3 mo of therapy. Treatment was well-tolerated with no instances of thrombosis. There was grade-1 neuropathy possibly related to drug in 1 subject. ≥Grade-3 thrombocytopenia/neutropenia occurred in 2 subjects. There was an anemia response in 10 (17%) subjects including 9 who became RBC-transfusion-independent. Median response-duration was 8+ mo (range, 6–13 mo). 14 of 24 subjecst (58%) with platelets ≤100 × 10e9/L had a >50% increment. There were no spleen responses. Anemia response occurred only in subjects with JAK2V617F (24% vs. 0; p=0.03) but was not correlated with mutant allele burden (p=0.39). Anemia response in JAK2V617F-positive subjects was predicted by the presence of pomalidomide-induced basophilia in the 1^st month of therapy (38% vs. 6%; p=0.02) or absence of marked splenomegaly (38% vs. 11%; p=0.05); response was not affected by cytogenetic risk-category (p=0.96) or WBC (p=0.27).

These data suggest that low-dose pomalidomide is effective in the treatment for anemia associated with JAK2V617F-positive myelofibrosis, especially in the absence of marked splenomegaly. Response appears to be predicted by early drug-induced basophilia. Pomalidomide also appears to improve thrombocytopenia in most subjects with baseline platelets <100 × 10e9/L but is not active in controlling disease-associated splenomegaly.

Mesa:SBio: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Incyte: Research Funding; Roche: Research Funding; eisai: Research Funding; telik: Research Funding.