Long-Term Follow-up of CALGB (Alliance) 100001: Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma

Abstract

CALGB (Alliance) 100001 was a phase II study evaluating autologous stem cell transplant (ASCT) followed by nonmyeloablative allogeneic stem cell transplant (alloSCT) in patients with multiple myeloma who had received no more than 18 months of prior therapy and had experienced no more than 1 prior progression event. Conditioning for ASCT was with high-dose melphalan (200 mg/m2). The alloSCT reduced-intensity conditioning (RIC) regimen consisted of fludarabine (30 mg/m2/d i.v. on days -7 through -3) and cyclophosphamide (1 g/m2/d i.v. on days -4 through -3). The primary objective was to determine the 6-month post-alloSCT treatment-related mortality (TRM) rate. Additional objectives included determining the proportion of patients who could complete this tandem ASCT-alloSCT approach in a cooperative group setting, overall response rates, rates of donor chimerism, rates of graft-versus-host disease (GVHD), disease-free survival, and overall survival (OS). Sixty patients were enrolled, of whom 57 (95%) completed ASCT and 49 (82%) completed tandem ASCT-alloSCT. The TRM rate was 2% (1/49; 90% confidence interval, 0.10% to 9.3%). Moderate to severe (grades 2 to 3) acute GVHD was observed in 13 of 49 alloSCT patients (27%). One patient died due to GVHD within 9 months of alloSCT. Twenty-seven of the 49 patients (55%) who underwent alloSCT reported chronic GVHD as either limited (15/49; 31%) or extensive (12/49; 24%) in the first year post-alloSCT and prior to the start of nonprotocol therapy for progressive disease. With a median follow-up for survival of 11 years, the median OS time is 6.6 years and the median time to disease progression is 3.6 years. Similar to other studies, this study confirmed that tandem ASCT/alloSCT is associated with durable disease control in a subset of patients. This study demonstrated the feasibility of performing tandem ASCT/alloSCT in a cooperative group setting and determined that a fludarabine/cyclophosphamide RIC regimen is associated with a very low TRM rate.

Trial registration: ClinicalTrials.gov NCT00028600.

Keywords: Allogeneic stem cell transplant; Autologous stem cell transplant; Multiple myeloma; Reduced-intensity conditioning.

Conflict of interest statement

Conflict of Interest:

SAH: has served on advisory boards for Adaptive Biotechnologies, Celgene, Genentech, Oncopeptides, Takeda; has served as a consultant for GSK, Celgene, Sorrento; has received research funding from Oncopeptides.

VJS: has nothing to disclose

KO: has nothing to disclose

KS: has nothing to disclose

DMB: has nothing to disclose

TCS: has nothing to disclose

TM: has served as a consultant for Roche, GSK and Legend; has received institutional research support from Sanofi, Amgen, Janssen and Seattle Genetics

MS: has nothing to disclose

RV: has received research funding from Bristol-Myers Squibb, Celgene, Takeda and has served on advisory boards/received honoraria from Janssen, Bristol-Myers Squibb, Celgene, Karyopharm, Sanofi, Genentech and secura bio.

BDC: has nothing to disclose

CL: has nothing to disclose

KCA: has served an advisory board member for Celgene, BMS, Millennium Takeda, Sanofi, Janssen, Gilead; is the founder of Oncopep and C4 Therapeutics.

PGR: has received research support from Oncopeptides, Celgene, Takeda, BMS and has served as an advisory committee member for Karyopharm, Oncopeptides, Celgene, Takeda, Janssen and Sanofi.

PLM: has received honoraria from Bristol-Myers Squibb, Celgene, Sanofi-Aventis, Takeda, Binding Site, research funding from Celgene, and has served on advisory committees/review panels/board membership for Bristol-Myers Squibb, Celgene, Sanofi-Aventis, Takeda, Binding Site, Karyopharm

Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

CONSORT flow diagram of patient disposition at the current data cut-off.

Figure 2.

Cumulative incidence of progression.

Figure 3.

Kaplan-Meier estimates of overall survival.