Phase 1/2 Trial of Carfilzomib Plus High-Dose Melphalan Preparative Regimen for Salvage Autologous Hematopoietic Cell Transplantation Followed by Maintenance Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma.

Abstract

We performed a phase 1/2 trial to investigate the safety and activity of the second-generation proteasome inhibitor Carfilzomib (K) on days -3/-2 in combination with melphalan 200 mg/m2 (MEL200) on day -2 (K-MEL) in patients with relapsed multiple myeloma (MM) undergoing autologous hematopoietic cell transplantation (phases 1 and 2). Patients without progression received 12 cycles of K maintenance at 36 mg/m2 days 1, 8, and 15 (schedule A) or days 1, 2, 15, and 16 (schedule B), with patients being treated for 2 cycles in each schedule and on the patient-preferred schedule for the remaining cycles (phase 2). The patients had received a median of 3 previous lines of therapy, 56% had undergone previous AHCT, and 51% had received previous K therapy. During phase 1 (n = 15), the maximum tolerated dose of K in combination with MEL200 was not reached, so the maximum tested dose of 27 mg/m2 (on day -3) and 56 mg/m2 (on day -2) was used in phase 2. The rate of very good partial response after K-MEL therapy (n = 44) was 59.2%, compared with 13.7% before K-MEL therapy. Among patients starting maintenance therapy (n = 27), 12-month progression-free survival was 66.7% and 12-month overall survival was 88.1%. There was no strong patient preference for either schedule. Two patients discontinued maintenance due to toxicity. K-MEL followed by K maintenance is safe and active salvage therapy in patients with MM.

• Authors: Luciano J Costa, Heather J Landau, Saurabh Chhabra, Parameswaran Hari, Racquel Innis-Shelton, Kelly N Godby, Mehdi Hamadani, Roni Tamari, Kate Anderton, Pamela Dixon, Sergio A Giralt
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 24 Issue 7 Pg. 1379-1385 (07 2018) ISSN: 1523-6536 [Electronic] United States
• PMID: 29410301 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Alkylating
• Oligopeptides
• carfilzomib
• Melphalan

Topics

• Aged
• Antineoplastic Agents, Alkylating (pharmacology, therapeutic use)
• Female
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Male
• Melphalan (pharmacology, therapeutic use)
• Middle Aged
• Multiple Myeloma (drug therapy, pathology)
• Oligopeptides (pharmacology, therapeutic use)
• Salvage Therapy (methods)
• Transplantation Conditioning (methods)
• Transplantation, Autologous (methods)