Phase I‐II trial of oral cyclophosphamide, prednisone and lenalidomide for the treatment of patients with relapsed and refractory multiple myeloma

Abstract

, 32 patients were entered in cohorts of three at three dose levels. The median age was 64 years, 59% were male, with a median two prior regimens. Responding patients could stay on treatment until progression. The full-dose CPR regimen produced no dose-limiting toxicity and was delivered for a median of 16 months (3Á5-65 months) with acceptable safety and tolerance. The overall response rate (≥ partial response) was 94% at a median follow up of 28 months. The median progression-free survival was 16Á1 months [95% confidence interval (CI); 10Á9-22Á5 months], while the median overall survival was 27Á6 months (95% CI; 16Á8-36Á6 months). Only the beta-2 microglobulin level at protocol entry correlated with a better survival (P = 0Á047). These observations compare favourably with other 2-and 3-drug combinations for relapsed/refractory myeloma, and suggest that CPR should be evaluated further in the setting of relapsed/refractory disease, or in newly diagnosed patients.

Pomalidomide, cyclophosphamide, and prednisone for relapsed/refractory multiple myeloma: a multicenter phase 1/2 open-label study

“…12,27,28 In our study, median PFS was 10.4 months and median OS was not reached, supporting the hypothesis that cyclophosphamide increased the clinical efficacy of pomalidomide.…”

Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma

“…[9][10][11][12][13][14][15] Interestingly, a combination of lenalidomide and continuous cyclophosphamide resulted in an ORR of 50% in lenalidomide refractory patients, suggesting cyclophosphamide may be able to overcome resistance to lenalidomide in the clinic. 16 In addition, Larocca et al combined continuous pomalidomide with oral cyclophosphamide.…”

Phase 1/2 study of lenalidomide combined with low-dose cyclophosphamide and prednisone in lenalidomide-refractory multiple myeloma

“…35 Other studies have also demonstrated a beneficial effect of addition of weekly cyclophosphamide to lenalidomide and corticosteroids in patients with relapsed/refractory lenalidomide-naive MM ($ PR: 65% to 94%). [40][41][42] Because of the high response and prolonged PFS reported in these studies, directly starting with the 3-drug regimen of lenalidomide, cyclophosphamide, and corticosteroid may also be considered, as opposed to adding cyclophosphamide at the time of development of lenalidomide-refractory disease. Furthermore, a retrospective analysis showed high efficacy ($ PR: 68%) and good tolerability of lenalidomide, low-dose cyclophosphamide, and prednisone in relapsed/refractory MM patients who were previously exposed to lenalidomide-dexamethasone (39% lenalidomide refractory).…”