Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study

Abstract

• Pomalidomide plus lowdose dexamethasone significantly improved PFS vs pomalidomide alone in relapsed and refractory multiple myeloma.• Pomalidomide plus low-dose dexamethasone is an important new treatment option for RRMM patients who have received multiple prior therapies.This multicenter, open-label, randomized phase 2 study assessed the efficacy and safety of pomalidomide (POM) with/without low-dose dexamethasone (LoDEX) in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ‡2 prior therapies (including lenalidomide [LEN] and bortezomib [BORT]) and had progressed within 60 days of their last therapy were randomized to POM (4 mg/day on days 1-21 of each 28-day cycle) with/without LoDEX (40 mg/week). The primary end point was progression-free survival (PFS). In total, 221 patients (median 5 prior therapies, range 1-13) received POM1LoDEX (n 5 113) or POM (n 5 108). With a median follow-up of 14.2 months, median PFS was 4.2 and 2.7 months (hazard ratio 5 0.68, P 5 .003), overall response rates (ORRs) were 33% and 18% (P 5 .013), median response duration was 8.3 and 10.7 months, and median overall survival (OS) was 16.5 and 13.6 months, respectively. Refractoriness to LEN, or resistance to both LEN and BORT, did not affect outcomes with POM1LoDEX (median PFS 3.8 months for both; ORRs 30% and 31%; and median OS 16 and 13.4 months). Grade 3-4 neutropenia occurred in 41% (POM1 LoDEX) and 48% (POM); no grade 3-4 peripheral neuropathy was reported. POM1LoDEX was effective and generally well tolerated and provides an important new treatment option for RRMM patients who have received multiple prior therapies. This trial was registered at www.clinicaltrials.gov as #NCT00833833. (Blood. 2014;123(12):1826-1832 Introduction Virtually all patients with multiple myeloma (MM) eventually relapse. Relapsed disease is characterized by increasingly shorter periods of remission following each salvage therapy.1 Survival among MM patients in whom novel agents (including bortezomib [BORT], lenalidomide [LEN], and/or thalidomide) have failed is especially poor.2 There is a clear unmet need for new treatments, particularly for patients who are relapsed and refractory to novel agents.Pomalidomide (POM) is a distinct immunomodulatory drug with potent antimyeloma activity.3-5 POM plus dexamethasone (DEX) has synergistic antiproliferative effects in LEN-resistant myeloma cells. 6 The activity of POM in cells resistant or refractory to LEN may be due to important differences in both the potency of the drugs and their respective mechanisms of action. 3,[7][8][9][10][11] POM has demonstrated efficacy in patients with relapsed/ refractory MM (RRMM) who had received multiple prior therapies, either when given alone [12][13][14] or with low-dose DEX (LoDEX). 14-17Here, we report the results of a multicenter, randomized, open-label, phase 2 trial. The phase 1 part of the study established the maximum tolerated dose of POM (4 mg/day on days 1-21 of a 28-day cycle). 18The phase 2 part evaluated the efficacy and s...

Venous thromboembolism in hematopoietic stem cell transplant recipients

“…Although pomalidomide has not been evaluated in the setting of consolidation after autologous HSCT, a 2% to 4% rate of VTE with thromboprophylaxis has been reported in the setting of relapsed/ refractory myeloma. [56][57][58] Thromboprophylaxis strategies have not been specifically evaluated in patients on maintenance therapy with novel immune-modulatory agents after transplant, however, studies in patients with newly diagnosed MM receiving lenalidomide or thalidomide-based treatments show a significant benefit of thromboprophylaxis. 59,60 Palumbo et al 59 randomly assigned 659 patients receiving thalidomide-based regimens to low-dose aspirin, warfarin or enoxaparin.…”

Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma

“…12 A phase 3 study of pomalidomide plus low-dose dexamethasone vs high-dose dexamethasone alone demonstrated a significant benefit to OS, PFS, and overall response rate (ORR). 13 Notably, subgroup analyses demonstrated a benefit to OS and PFS in lenalidomide-refractory patients treated with pomalidomide plus low-dose dexamethasone vs high-dose dexamethasone.…”

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

“…These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. Philippe Moreau, 7 Anne Banos, 8 Albert Oriol, 9 Laurent Garderet, 10 Michele Cavo, 11 Valentina Ivanova, 12 Adrian Alegre, 13 Joaquin Martinez-Lopez, 14 Christine Chen, 15 Christoph Renner, 16 Nizar Jacques Bahlis, 17 Xin Yu, 18 Terri Teasdale, the management of patients who have exhausted treatment with BORT, LEN, and THAL. In the treatment of RRMM, the decision whether to switch agent classes (i.e.…”