Faculty Collaboration Database

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. Biol Blood Marrow Transplant 2018 Jul;24(7):1379-1385

Date

02/08/2018

Pubmed ID

29410301

Pubmed Central ID

PMC7590532

DOI

10.1016/j.bbmt.2018.01.036

Scopus ID

2-s2.0-85046706138 (requires institutional sign-in at Scopus site)   17 Citations

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.

Author List

Costa LJ, Landau HJ, Chhabra S, Hari P, Innis-Shelton R, Godby KN, Hamadani M, Tamari R, Anderton K, Dixon P, Giralt SA

Authors

Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Antineoplastic Agents, Alkylating
Female
Hematopoietic Stem Cell Transplantation
Humans
Male
Melphalan
Middle Aged
Multiple Myeloma
Oligopeptides
Salvage Therapy
Transplantation Conditioning
Transplantation, Autologous