Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide–refractory multiple myeloma: Intergroupe Francophone du Myélome 2009-02

Abstract

Key Points• Combination of pomalidomide with dexamethasone is highly active and can salvage end stage myeloma refractory to lenalidomide and bortezomib.• Current data suggest pomalidomide 4 mg/day on days 1 to 21 per 28-days cycle with dexmethasone should be studied in future phase 3 trials.The combination of pomalidomide and dexamethasone can be safely administered to patients with multiple myeloma (MM) and has significant efficacy, although the optimal regimen remains to be determined. Patients with MM whose disease progressed after multiple lines of therapy have limited treatment options. We designed a multicenter, phase 2 randomized study assessing two different dose regimens of pomalidomide and dexamethasone in advanced MM. Treatment response was assessed centrally. Pomalidomide (4 mg) was given orally on days 1 to 21 (arm 21/28) or continuously (arm 28/28) over a 28-day cycle, plus dexamethasone given weekly. Eighty-four patients (43, arm 21/28 and 41, arm 28/28) were randomized. The median number of prior lines was 5. Overall response rate was 35% (arm 21/28) and 34% (arm 28/28), independent of the number of prior lines and level of refractoriness. Median duration of response, time to disease progression, and progression-free survival was 7.3, 5.4, and 4.6 months, respectively, which was similar across cohorts. At 23 months follow-up, median overall survival was 14.9 months, with 44% of the patients alive at 18 months. Toxicity consisted primarily of myelosuppression, which was manageable. The efficacy and safety data presented here, along with data from other phase 2 trials, suggest that pomalidomide 4 mg per day on days 1 to 21 of 28 with dexamethasone should be investigated in future trials. This trial is registered at ClinicalTrials.gov (No.

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.…”

Limiting early mortality: Do's and don'ts in the management of patients with newly diagnosed multiple myeloma

“…Much of the recently obtained success in the management of patients with multiple myeloma (MM) can be linked to strategies that deepen and prolong initial remission and/or more effectively treat relapsed disease: broader use of autologous hematopoietic progenitor cells transplantation (AHPCT) [1,2], use of proteasome inhibitors and immunomodulatory drugs (IMIDs) in induction, consolidation and maintenance [3][4][5][6][7][8][9], and sequential therapy with a growing number of approved and experimental agents in the relapsed setting [10][11][12][13][14]. In this scenario, MM is often presented as a chronic condition compatible with many years of survivorship with good quality of life before patients ultimately succumb to refractory disease [15].…”

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

“…Consistent with the established tolerability profile of POM + LoDEX, 18-21 the most common grade 3/4 adverse events observed for POM + LoDEX were hematologic (neutropenia, anemia, and thrombocytopenia). [8][9][10][11][12][13][14][15][16][17][18][19][20][21] The current publication reports efficacy from the MM-003 trial by depth of response, number of prior therapies, and types of prior therapies in the MM-003 trial.…”