Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma: Results of the BMT CTN 0702 Trial

Abstract

Purpose: Single-cycle melphalan 200 mg/m² and autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide (len) maintenance have improved progression-free survival (PFS) and overall survival (OS) for transplantation-eligible patients with multiple myeloma (MM). We designed a prospective, randomized, phase III study to test additional interventions to improve PFS by comparing AHCT, tandem AHCT (AHCT/AHCT), and AHCT and four subsequent cycles of len, bortezomib, and dexamethasone (RVD; AHCT + RVD), all followed by len until disease progression.

Patients and methods: Patients with symptomatic MM within 12 months from starting therapy and without progression who were age 70 years or younger were randomly assigned to AHCT/AHCT + len (n = 247), AHCT + RVD + len (n = 254), or AHCT + len (n = 257). The primary end point was 38-month PFS.

Results: The study population had a median age of 56 years (range, 20 to 70 years); 24% of patients had high-risk MM, 73% had a triple-drug regimen as initial therapy, and 18% were in complete response at enrollment. The 38-month PFS rate was 58.5% (95% CI, 51.7% to 64.6%) for AHCT/AHCT + len, 57.8% (95% CI, 51.4% to 63.7%) for AHCT + RVD + len, and 53.9% (95% CI, 47.4% to 60%) for AHCT + len. For AHCT/AHCT + len, AHCT + RVD + len, and AHCT + len, the OS rates were 81.8% (95% CI, 76.2% to 86.2%), 85.4% (95% CI, 80.4% to 89.3%), and 83.7% (95% CI, 78.4% to 87.8%), respectively, and the complete response rates at 1 year were 50.5% (n = 192), 58.4% (n = 209), and 47.1% (n = 208), respectively. Toxicity profiles and development of second primary malignancies were similar across treatment arms.

Conclusion: Second AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with MM did not improve PFS or OS. Single AHCT and len should remain as the standard approach for this population.

Trial registration: ClinicalTrials.gov NCT01109004.

FIG 1.

CONSORT diagram. (*) Sites were not required to register patients who signed informed consent but did not enroll. AHCT, autologous hematopoietic cell transplantation; RVD, lenalidomide, bortezomib, and dexamethasone.

FIG 2.

(A) Progression-free survival, (B) overall survival, and (C) disease progression in the tandem autologous hematopoietic cell transplantation (AHCT) + lenalidomide (len), AHCT + len, bortezomib, and dexamethasone (RVD) + len and AHCT + len arms.

FIG 3.

Hazard ratios (HR) from (A) progression-free survival and (B) overall survival analyses using separate Cox proportional hazard models that included random assignment risk strata and treatment group. AHCT, autologous hematopoietic cell transplantation; RVD, lenalidomide, bortezomib, and dexamethasone.

FIG 4.

Event-free survival in the tandem autologous hematopoietic cell transplantation (AHCT) + lenalidomide (len), AHCT + len, bortezomib, and dexamethasone (RVD) + len, and AHCT + len arms.