Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma

Abstract

Key Points• In a multicenter, randomized phase 3 trial, MPR-R was not superior over MPT-T with respect to response rate, PFS, and OS.• Grade 3/4 hematologic toxicity requiring growth factor support occurred with MPR-R vs clinically significant neuropathy with MPT-T.The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/ NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95% confidence interval [CI], 18-23 months) vs 23 months (95% CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95% CI, 0.72-1.04; P 5 .12). Response rates were similar, with at least a very good partial response of 47% and 45%, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64% vs 27%. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16% vs 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance vs myelosuppression with

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

“…In contrast, melphalan has more profound myelosuppression, making this alkylating agent less attractive to use in combination with lenalidomide. 33,34 Nonhematologic toxicity of REP consisted mainly of infections. Discontinuations because of adverse events were uncommon, allowing patients to continue therapy until disease progression.…”

Therapy for Relapsed Multiple Myeloma

“…Apart from its established use as the conditioning agent of choice before ASCT, it has been studied in combination with IMiDs 45,90–92 and PIs 46,93,94 both for induction of newly diagnosed myeloma and in the relapsed setting, the latter in combination with panobinostat. 95 It is reserved for patients who are not candidates for ASCT.…”

Venous thromboembolism risk with contemporary lenalidomide‐based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta‐analysis

“…During the initial clinical experience with thalidomide, a first‐generation IMiD, a signal for higher risk of VTE was identified in several studies . Lenalidomide (Len) is a second‐generation IMiD that largely has replaced thalidomide in the United States because of its better toxicity profile and higher efficacy . However, Len is also associated with a high incidence of VTE.…”