Phase1/‐2 study of Pomalidomide in myelofibrosis

Mesa, Ruben A.; Pardanani, Animesh; Hussein, Kebede; Wu, Wenting; Schwager, Susan M.; Litzow, Mark R.; Tefferi, Ayalew

doi:10.1002/ajh.21598

Cited by 87 publications

(79 citation statements)

References 16 publications

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“…The current study includes all Mayo Clinic patients who participated in two consecutive clinical trials using pomalidomide-based therapy for MF (ClinicalTrials.gov Identifiers: NCT00463385 and NCT00669578) [4,14,15]. All studies were approved by the Mayo Clinic Institutional Review Board and supported by Celgene Corporation, Summit, NJ, USA.…”

Section: Methodsmentioning

confidence: 99%

“…P values less than 0.05 were considered significant. included pomalidomide; 19 were enrolled in a phase-1 dose escalation study (2.5-3.5 mg/day) [14], 58 in an extension of the phase-1 study using low-dose single agent pomalidomide (0.5 mg/day) [15], and 17 in a phase-2 randomized study (2 mg/day alone or either 2 or 0.5 mg/ day in combination with a short course of prednisone Comparison of survival data between 72 pomalidomide-treated patients with primary myelofibrosis (PMF) and 471 PMF patients not exposed to pomalidomide therapy. The two study populations were matched for their Dynamic International Prognostic Scoring System (DIPSS)-plus [18] risk profile (only patients with high or intermediate-2 risk disease were considered), hemoglobin and platelet counts that were consistent with study eligibility criteria (all patients had a hemoglobin level of <10 g/dL and platelet count of >20 3 10 9 /L).…”

Section: Methodsmentioning

confidence: 99%

“…therapy) [4]. Patient characteristics at study entry are outlined in Table I and additional patient and protocol details are as previously described [4,14,15]. Follow-up information was updated in August, 2011 (median time from drug initiation was 27 months; range 20-52 months).…”

Section: Methodsmentioning

confidence: 99%

“…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].…”

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Long‐term outcome of pomalidomide therapy in myelofibrosis

et al. 2011

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Ninety-four Mayo Clinic patients with myelofibrosis (MF) participated in two consecutive clinical trials of pomalidomide (0.5-3.5 mg/day), with or without prednisone. Overall anemia response was 27% and increased to 53% in JAK2V617F-positive patients with <10 cm palpable splenomegaly and <5% circulating blasts; response rate was 0% in mutation-negative patients with either 10 cm splenomegaly or 5% circulating blasts (P 5 0.0001). Median duration of anemia response was 16 months. Treatment effect on splenomegaly was negligible. To date, pomalidomide therapy has been discontinued in 86 (91%) patients at a rate of 68% at 1 year and 89% at 2 years. Grade 1 sensory neuropathy developed in 4 (13%) of 30 patients treated for 1 year. Risk-adjusted survival in pomalidomide-treated primary MF patients (n 5 72) was similar to their counterparts not exposed to the drug (n 5 471; P 5 0.19). Long-term follow-up of pomalidomide treatment in MF reveals palliative value for a select group of patients and treatment-emergent sensory neuropathy. Am. J. Hematol. 87:66-68, 2012. V V C 2011 Wiley Periodicals, Inc. IntroductionPomalidomide is an immunomodulatory drug that is structurally related to both lenalidomide and thalidomide [1]. All three drugs display anti-angiogenic, anti-tumor necrosis factor-a, and T cell modulatory effect, but the precise mechanism of action in vivo is poorly understood. Thalidomide [2], lenalidomide [3], and pomalidomide [4] have all been shown to have therapeutic activity in myelofibrosis (MF), including primary (PMF), post-polycythemia vera (post-PV MF), and post-essential thrombocythemia (post-ET MF). Higher doses (100-400 mg/day) of thalidomide were associated with an increased adverse drop-out rate whereas low-dose (50 mg/day) thalidomide, alone or in combination with prednisone, was better tolerated and alleviated anemia in approximately 20% of treated patients with MF [5][6][7]. Lenalidomide (5-10 mg/day), with or without prednisone, also alleviated anemia in a similar proportion of patients with MF [3,8,9], and was most useful in the presence of del(5q) [10]. Two recent studies reassessed treatment response using the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria [11]; one study reported up to 38% response rate for lenalidomide plus prednisone therapy [12] whereas the other study reported 28% response rate for thalidomide-based therapy [13]. 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...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Long‐term outcome of pomalidomide therapy in myelofibrosis

et al. 2011

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“…17 The maximum tolerated dose of pomalidomide was 2 mg/day in relapsed or refractory multiple myeloma 18 and 3 mg/day in MF. 19 At 2 mg/day, the drug, in combination with dexamethasone, has shown remarkable activity in relapsed multiple myeloma, including patients refractory to either lenalidomide or bortezomib. 20 In a phase-2 randomized study (n ¼ 84), pomalidomide either alone (2 mg/day) or in combination with prednisone (0.5 or 2 mg/day) was shown to be safe (no neuropathy and o10% severe myelosuppression) and effective (25% response rate) in treating anemia associated with MF.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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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.

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