A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence

Abstract

RBC-transfusion dependence is common in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis. The objective of this study was to determine the rates of RBC-transfusion independence after therapy with pomalidomide vs placebo in persons with MPN-associated myelofibrosis and RBC-transfusion dependence. Two hundred and fifty-two subjects (intent-to-treat (ITT) population) including 229 subjects confirmed by central review (modified ITT population) were randomly assigned (2:1) to pomalidomide or placebo. Trialists and subjects were blinded to treatment allocation. Primary end point was proportion of subjects achieving RBC-transfusion independence within 6 months. One hundred and fifty-two subjects received pomalidomide and 77 placebo. Response rates were 16% (95% confidence interval (CI), 11, 23%) vs 16% (8, 26% P=0.87). Response in the pomalidomide cohort was associated with ⩽4 U RBC/28 days (odds ratio (OR)=3.1; 0.9, 11.1), age ⩽65 (OR=2.3; 0.9, 5.5) and type of MPN-associated myelofibrosis (OR=2.6; 0.7, 9.5). Responses in the placebo cohort were associated with ⩽4 U RBC/28 days (OR=8.6; 0.9, 82.3), white blood cell at randomization >25 × 109/l (OR=4.9; 0.8, 28.9) and interval from diagnosis to randomization >2 years (OR=4.9; 1.1, 21.9). Pomalidomide was associated with increased rates of oedema and neutropenia but these adverse effects were manageable. Pomalidomide and placebo had similar RBC-transfusion-independence response rates in persons with MPN-associated RBC-transfusion dependence.

Emerging treatments for classical myeloproliferative neoplasms

“…35 A phase 1-2 study of pomalidomide reported responses in up to 36% of the patients in association with prednisone 36 ; unfortunately, a phase 3 study failed confirm these results. 37 …”

Safety considerations when treating myelofibrosis

“…Pomalidomide has shown similar results for anaemia improvement of 25% (+/-prednisolone) but was better tolerated (≥grade 3 neutropenia (8%) and thrombocytopenia (11%) [68]. Unfortunately, in a phase 3 study known as RESUME, pomalidomide was not superior to placebo for improving anaemia [83].…”

Anemia in myelofibrosis—prevalence, the U2AF1 connection, new treatments

“…Among these, the latter three are the most recent inductees, with only pomalidomide so far receiving Food and Drug Administration approval for the treatment of advanced multiple myeloma. In a recently published phase-3 study involving patients with myelofibrosis 5 , pomalidomide was not significantly better than placebo in providing relief from red cell transfusion dependency. These results were different from those of a previously reported non-controlled study 6 , where pomalidomide displayed antianemia activity, in a subset of JAK2 -mutated patients with myelofibrosis, in the absence of marked splenomegaly or excess circulating blasts.…”