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

• Published in: Journal of clinical oncology Vol. 37; no. 7; pp. 589 - 597
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 01.03.2019
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bortezomib - administration & dosage; Bortezomib - adverse effects; Consolidation Chemotherapy; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Disease Progression; Female; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - mortality; Humans; Lenalidomide - administration & dosage; Lenalidomide - adverse effects; Maintenance Chemotherapy; Male; Melphalan - administration & dosage; Middle Aged; Multiple Myeloma - mortality; Multiple Myeloma - pathology; Multiple Myeloma - therapy; Myeloablative Agonists - administration & dosage; ORIGINAL REPORTS; Progression-Free Survival; Prospective Studies; Remission Induction; Reoperation; Time Factors; Transplantation, Autologous; United States; Young Adult; United States
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/jco.18.00685

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 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. 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. 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.