A phase-2 trial of low-dose pomalidomide in myelofibrosis

Abstract

In a previous study, we reported on the safety and efficacy of low-dose (0.5 mg) pomalidomide and prednisone and pomalidomide alone (2 mg/day), for the treatment of anemia associated with myelofibrosis (MF). The current study examined the value of low-dose pomalidomide alone. The main eligibility criterion was transfusion-dependency or hemoglobin o10 gm per 100 ml. Anemia response was assessed by International Working Group criteria. Pomalidomide (0.5 mg/ day) was given to 58 patients (median age 68 years); 46 (79%) were transfusion-dependent and 42 were JAK2V617F positive. Anemia response was documented only in the presence of JAK2V617F (24 vs 0%; P ¼ 0.03) but was not further affected by mutant allele burden (P ¼ 0.39); 9 of the 10 anemia responders became transfusion independent. Anemia response in JAK2V617F-positive patients was predicted by the presence of pomalidomide-induced basophilia in the first month of therapy (38 vs 6%; P ¼ 0.02) or absence of marked splenomegaly (38 vs 11%; P ¼ 0.05). A total of 14 (58%) of 24 patients with a platelet count of p100 Â 10 9 cells/l experienced a 450% increment in platelet count. There were no spleen responses. Grade 3 or 4 thrombocytopenia/neutropenia occurred in 2% / 0% of patients. Low-dose pomalidomide is effective in the treatment of anemia associated with JAK2V617F-positive MF; response is predicted by early drug-induced basophilia.

One Thousand Patients With Primary Myelofibrosis: The Mayo Clinic Experience

“…For example, more than half of the patients were symptomatically anemic (ie, hemoglobin Ͻ10 g/dL) at time of referral and 38% required red blood cell transfusions, underscoring the dire need for an antianemia drug in PMF. 37,38 The particular information also points out the limitations of drugs that display anemia as an adverse effect, which is a recurrent issue with certain JAK inhibitors. 24,25 The study also suggests that about a third of patients present with marked splenomegaly or constitutional symptoms and might, therefore, benefit from JAK inhibitor therapy.…”

Long‐term outcome of pomalidomide therapy in myelofibrosis

“…In a phase-2 randomized study, pomalidomide alone at 2 mg/day was shown to be as active (23% response rate), in the treatment of anemia, as prednisone plus pomalidomide at 0.5 (36% response rate) or 2 mg/day (16% response rate) [4]. In an extension of the above-mentioned phase-1 study [15], low-dose pomalidomide (0.5 mg/day), as a single agent, was given to 58 patients and induced a 17% anemia response, which was predicted by the absence of marked splenomegaly, presence of JAK2V617F, and lower circulating levels of monocyte chemotactic protein-1, interleukin (IL)-2R, IL-15, and IL-8 [16]. Pomalidomide treatment was also beneficial in terms of alleviating thrombocytopenia but its effect on splenomegaly was negligible.…”

“…We have recently communicated the short-term results of two consecutive clinical trials using pomalidomide therapy for MF [4,14,15]. The maximum tolerated dose of pomalidomide in MF was 3 mg/day (dose-limiting toxicity was myelosuppression) but doses higher than 2 mg/day were associated with more myelosuppression and other toxicities and were not necessarily more effective [15].…”

“…In a phase-2 randomized study, pomalidomide alone at 2 mg/day was shown to be as active (23% response rate), in the treatment of anemia, as prednisone plus pomalidomide at 0.5 (36% response rate) or 2 mg/day (16% response rate) [4]. In an extension of the above-mentioned phase-1 study [15], low-dose pomalidomide (0.5 mg/day), as a single agent, was given to 58 patients and induced a 17% anemia response, which was predicted by the absence of marked …”

“…However, in a prospective multi-center study [8], the combination of lenalidomide and prednisone resulted in only 19% anemia response and 23% overall response. Regardless, the use of thalidomide or lenalidomide in MF is limited by the respective occurrence of peripheral neuropathy [12] and moderate to severe myelosuppression [8], in the majority of treated patients.We have recently communicated the short-term results of two consecutive clinical trials using pomalidomide therapy for MF [4,14,15]. The maximum tolerated dose of pomalidomide in MF was 3 mg/day (dose-limiting toxicity was myelosuppression) but doses higher than 2 mg/day were associated with more myelosuppression and other toxicities and were not necessarily more effective [15].…”