Long‐term outcome of pomalidomide therapy in myelofibrosis

Abstract

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...

One Thousand Patients With Primary Myelofibrosis: The Mayo Clinic Experience

“…The corresponding figures for patients seen 35 and pomalidomide. 36 The current study also provides valuable information regarding the proportion of patients with PMF who present with adverse risk factors and with disease aspects that significantly compromise quality of life. 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.…”

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

“…subsequent phase 2 study of single agent pomalidomide, anemia response was documented only in the presence of JAK2V617F (24% vs. 0%) [135,136]. Platelet response was seen in 58% of patients but the drug had limited activity in reducing spleen size.…”

How I treat polycythemia vera

“…[85][86][87][88] For the control of myeloproliferation and symptoms in post-PV MF, HU is mostly ineffective almost all in patients treated with HU during PV phase.…”