Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma: Results of the BMT CTN 0702 Trial. J Clin Oncol 2019 Mar 01;37(7):589-597
Date
01/18/2019Pubmed ID
30653422Pubmed Central ID
PMC6553842DOI
10.1200/JCO.18.00685Scopus ID
2-s2.0-85064136756 (requires institutional sign-in at Scopus site) 177 CitationsAbstract
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.
Author List
Stadtmauer EA, Pasquini MC, Blackwell B, Hari P, Bashey A, Devine S, Efebera Y, Ganguly S, Gasparetto C, Geller N, Horowitz MM, Koreth J, Knust K, Landau H, Brunstein C, McCarthy P, Nelson C, Qazilbash MH, Shah N, Vesole DH, Vij R, Vogl DT, Giralt S, Somlo G, Krishnan AAuthors
Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of WisconsinMary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdultAged
Antineoplastic Combined Chemotherapy Protocols
Bortezomib
Consolidation Chemotherapy
Dexamethasone
Disease Progression
Female
Hematopoietic Stem Cell Transplantation
Humans
Maintenance Chemotherapy
Male
Melphalan
Middle Aged
Multiple Myeloma
Myeloablative Agonists
Prospective Studies
Remission Induction
Reoperation
Time Factors
Transplantation, Autologous
United States
Young Adult