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

A Tefferi, H K Al-Ali, G Barosi, T Devos, H Gisslinger, Q Jiang, J-J Kiladjian, R Mesa, F Passamonti, M F McMullin, V Ribrag, G Schiller, A M Vannucchi, D Zhou, D Reiser, J Zhong, R P Gale, A Tefferi, H K Al-Ali, G Barosi, T Devos, H Gisslinger, Q Jiang, J-J Kiladjian, R Mesa, F Passamonti, M F McMullin, V Ribrag, G Schiller, A M Vannucchi, D Zhou, D Reiser, J Zhong, R P Gale

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.

Trial registration: ClinicalTrials.gov NCT01178281.

Conflict of interest statement

HKA-A has received honoraria, research funding and travel expenses from Celgene and Novartis and has acted as a consultant for Novartis; J-JK has acted as a consultant for AOP Orphan and Novartis and received research funding from AOP Orphan; RM has received honoraria from Novartis, received research funding from Celgene, CTI, Gilead and Promedia and acted as a consultant for Ariad and Galena; VR has acted as a consultant for BMS, Gilead, Infinity, Nanostring, PharmaMar and Servier, received honoraria and research funding from ESAI and received travel expenses from Roche; GS has been on a speakers bureau and received research funding from Celgene; AMV has been a member of a board of directors, been on a speakers bureau and received research funding from Novartis; DR and JZ are employed by and own stock or other equity in Celgene Corp.; RPG is a part-time employee of Celgene Corp. and owns stock or other equity of Celgene Corp. RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CONSORT flow diagram.

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Source: PubMed

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