Combined bendamustine, prednisolone and thalidomide for refractory or relapsed multiple myeloma after autologous stem‐cell transplantation or conventional chemotherapy: results of a Phase I clinical trial

Abstract

Summary Thalidomide is an effective agent for advanced refractory or relapsed multiple myeloma (MM), although dose‐limiting toxicity (DLT) may limit its use. This Phase I study found that a combination of low‐dose thalidomide with bendamustine and prednisolone (BPT) maintained or increased efficacy, whilst avoiding DLT in 28 patients with MM that was refractory or that had relapsed after conventional chemotherapy or high‐dose therapy with stem‐cell support. BPT comprised fixed doses of bendamustine (60 mg/m2) and prednisolone (100 mg), and escalating doses of thalidomide (50, 100, 200 mg). Treatment cycles were repeated every 28 d until the occurrence of maximum response, DLT, or disease progression. Twenty‐four patients responded after at least two cycles (four complete remission, six very good partial remission, 14 partial remission). Median progression‐free and overall survival for all patients was 11 and 19 months respectively. Only mild/moderate non‐haematological side effects were observed and no patient developed dose‐limiting haematotoxicity. Transient grade 3–4 neutropenia was reported in 12 patients, and grade 3–4 thrombocytopenia occurred in two patients. We conclude that BPT therapy was well tolerated in patients with relapsed or refractory MM, with a response rate higher than 80%. The maximum tolerated dose of thalidomide was not reached in this study.

Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study

“…12 Ponisch et al performed a phase 1 clinical trial testing the combination of bendamustine, prednisolone, and thalidomide for relapsed or refractory MM after autologous SCT or conventional chemotherapy. 13 Using fixed doses of bendamustine (60 mg/m 2 ) and prednisolone (100 mg) with escalating doses of thalidomide (50, 100, and 200 mg), the response rate was 86% with 14% CRs, but a direct comparison with our data is difficult because of the use of different response criteria without free light chains for response assessment. 21 Further, patients in this trial were lenalidomide-and bortezomib-naive and were less heavily pretreated.…”

“…The ORR in this study was 86%. 13 Given the different mechanisms of action ascribed to lenalidomide and bendamustine, as well as results from previous studies successfully combining immunomodulatory drugs and alkylating agents, such as MP plus thalidomide or MP plus lenalidomide, [14][15][16] we sought to assess the feasibility and efficacy of a regimen combining bendamustine and lenalidomide. In addition, we wanted to explore whether this combination has efficacy in patients with prior exposure to lenalidomide.…”

Toxicity-reduced, myeloablative allograft followed by lenalidomide maintenance as salvage therapy for refractory/relapsed myeloma patients

“…Novel active drugs have improved the treatment options for myeloma patients. [16][17][18][19][20] Salvage treatment with lenalidomide/ dexamethasone for relapsed/refractory patients resulted in a median PFS and OS of about 11 and 22 months, respectively. 16,18 A recent prospective trial performed by the EBMT with melphalan-/fludarabine-based, dose-reduced conditioning and allograft from unrelated donors resulted in a similar median PFS and OS but the Kaplan-Meier curve suggests a plateau after 5 years at about 20%.…”

Carmustine replacement in intensive chemotherapy preceding reinjection of autologous HSCs in Hodgkin and non-Hodgkin lymphoma: a review

“…[21][22][23][24] Bendamustine is effective against indolent lymphomas, 25,26 chronic lymphocytic leukemia, mantle cell lymphoma, 27 large B-cell lymphomas, 28 peripheral T-cell lymphomas, 29,30 HLs [31][32][33] and multiple myelomas. [34][35][36] The doses used are 50-180 mg/m 2 on days 1 and 2 or a total dose of 100-360 mg/m 2 in a single intravenous perfusion over 30-60 min every 21-28 days. Digestive disorders and increased infectious toxicities were associated with higher doses.…”