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Blood and Marrow Transplant Clinical Trials Network A Trial of Single Autologous Transplant With or Without Consolidation Therapy Versus Tandem Autologous Transplant With Lenalidomide Maintenance for Patients With Multiple Myeloma (BMT CTN-0702-BioLINCC)

Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.

Objectives: To compare the use of tandem autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide maintenance, AHCT plus four cycles of lenalidomide, bortezomib, and dexamethasone (RVD) followed by lenalidomide, and AHCT and lenalidomide only in improving outcomes for patients with active multiple myeloma (MM).

Background: At the time of this trial, initial myeloma reductive therapy followed by high-dose melphalan plus AHCT with long-term lenalidomide was the standard of care for patients newly diagnosed with MM in the United States. Despite substantive improvements in outcomes with the addition of lenalidomide, most patients still experienced disease progression and ultimately died as a result of the disease. Several approaches to further improve outcome after initial AHCT have been investigated but incremental benefit compared with maintenance therapy remains to be determined. This trial was initiated to assess whether the additional interventions of second AHCT or RVD consolidation to AHCT and lenalidomide further improve outcomes.

Participants: Patients with symptomatic MM who were 70 years old or younger, had a Karnofsky score equal to or greater than 70, received at least two cycles of any regimen as initial systemic therapy without disease progression, and were within 2 to 12 months of the first dose of initial therapy were eligible.

758 patients were enrolled. 247 patients were randomly assigned to the AHCT/AHCT + lenalidomide arm, 254 patients to the AHCT + RVD + lenalidomide arm, and 257 patients to the AHCT + lenalidomide arm.

Design: The BMT CTN-0702 study was a Phase III multicenter trial. All patients were randomly assigned in a 1:1:1 manner at the time of enrollment, which occurred within 7 days before the first high-dose melphalan conditioning regimen. Random assignment was stratified by disease risk and transplantation center. High-risk MM was defined by presence of high β2-microglobulin, presence of cytogenetic abnormalities, or aneuploidy. Patients without cytogenetic analysis available and low β2-microglobulin level (≤5.5 mg/L) or with deletion 13 detected by fluorescence in situ hybridization were classified as standard risk.

All enrolled patients were to receive high-dose melphalan (200 mg/m2) followed by mobilized autologous peripheral-blood stem-cell infusion (minimum 2 × 106 CD34+ cells/kg). Subsequent therapy was based on random assignment at the time of enrollment. The second phase of therapy started between 60 and 120 days after the first AHCT, once patients had sufficiently recovered. Patients randomly assigned to a second transplantation received high-dose melphalan (200 mg/m2) followed by autologous peripheral-blood stem-cell infusion. Patients randomly assigned to RVD consolidation received four cycles of lenalidomide 15 mg/d on days 1 to 14; bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of every 21-day cycle; and dexamethasone 40 mg per day on days 1, 8, and 15. After their initial interventions, all patients received lenalidomide starting at 10 mg per day for 3 months and increasing to 15 mg per day. Dose adjustments for toxicity were permitted. Maintenance therapy was initially designed to be given for 3 years to all patients. An amendment expanded use of lenalidomide to continue until toxicity, disease progression, or withdrawal of consent.

Quality of life was assessed using the Short Form 36 and Functional Assessment of Cancer Therapy-Bone Marrow Transplant at baseline and yearly.

The primary study end point was progression free survival at 38 months.

Conclusions: Second AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with multiple myeloma did not improve progression free survival or overall survival. Single AHCT and lenalidomide should remain as the standard approach for this population.