Lenalidomide Plus Melphalan Without Prednisone for Previously Untreated Older Patients With Multiple Myeloma: A Phase II Trial

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• 作者：Darrell J. White¹ ; ^{d.white@dal.ca} ; Nizar J. Bahlis² ; Deb C. Marcellus³ ; Andrew Belch⁴ ; A. Keith Stewart⁵ ; Christine Chen⁶ ; Michael J. Kovacs⁷ ; David A. Macdonald¹ ; Donna E. Reece⁶ ; Tony Reiman⁸ ; Erica Harnett⁹ ; Ralph M. Meyer⁹ ; Judy-Anne W. Chapman⁹ ; Stephen Couban¹
• 关键词：Corticosteroids ; Lenalidomide ; Melphalan ; Multiple myeloma ; Phase II trial
• 刊名：Clinical Lymphoma Myeloma and Leukemia
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：13
• 期：1
• 页码：19-24
• 全文大小：273 K

文摘

Background

We conducted a phase II trial that evaluated the tolerability and efficacy of combining lenalidomide with melphalan in previously untreated patients with multiple myeloma who were not candidates for autologous stem cell transplantation.

Methods

After a run-in phase of 6 patients, we planned to conduct a randomized phase II selection-design trial that assessed 2 dose levels of lenalidomide, given days 1 to 21, combined with melphalan, given days 1 to 4, and every 28 days. Planned doses of melphalan were 9 mg/m²/d and respective doses of lenalidomide were 10 and 20 mg/d (M9L10 and M9L20). Coprimary endpoints were the frequency of dose-limiting Planned doses of melphalan were 9 mg/m²/d and respective doses of lenalidomide were 10 and 20 mg/d (M9L10 and M9L20). toxicities (DLT) and complete response (CR).

Results

Four patients received M9L10; all experienced DLTs, which resulted in closure of this cohort. When using the same schedule, we then sequentially tested M6L10 (melphalan 6 mg/m² on days 1 to 4 and lenalidomide 10 mg/d on days 1 to 21 every 28 days) (6 patients), M4L15 (melphalan 4 mg/m² on days 1 to 4 and lenalidomide 15 mg/d on days 1 to 21 every 28 days) (6 patients), and M5L10 (melphalan 5 mg/m² days 1 to 4 and lenalidomide 10 mg/d days 1 to 21 every 28 days) (34 patients). In each cohort, the DLT endpoint was reached because of severe and prolonged hematologic toxicity. At the final dose level, M5L10, 20 of 27 patients experienced DLTs within their first 3 cycles; among 10 patients who received at least 6 cycles, none achieved a CR.

Conclusions

Combining lenalidomide plus melphalan without prednisone is associated with substantial hematologic toxicity that precludes cyclical administration of adequate drug doses.