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

Publication Type
Journal Article
Year of Publication
Stadtmauer, Edward A; Pasquini, Marcelo C; Blackwell, Beth; Hari, Parameswaran; Bashey, Asad; Devine, Steven; Efebera, Yvonne; Ganguly, Siddharta; Gasparetto, Cristina; Geller, Nancy; Horowitz, Mary M; Koreth, John; Knust, Kristin; Landau, Heather; Brunstein, Claudio; McCarthy, Philip; Nelson, Courtney; Qazilbash, Muzaffar H; Shah, Nina; Vesole, David H; Vij, Ravi; Vogl, Dan T; Giralt, Sergio; Somlo, George; Krishnan, Amrita
J Clin Oncol
Date Published
2019 03 01
Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Consolidation Chemotherapy; Dexamethasone; Disease Progression; Female; Hematopoietic Stem Cell Transplantation; Humans; Lenalidomide; Maintenance Chemotherapy; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Progression-Free Survival; Prospective Studies; Remission Induction; Reoperation; Time Factors; Transplantation, Autologous; United States; Young Adult

PURPOSE: Single-cycle melphalan 200 mg/m 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.