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.

Bortezomib consolidation following autologous transplant in younger and older patients with newly diagnosed multiple myeloma in two phase III trials

“…Our analyses also demonstrated that, on multivariate analysis, 32 Similar findings were reported from a metaanalysis of consolidation plus lenalidomide maintenance vs lenalidomide maintenance alone, 33 although preliminary findings from the EMN02/HOVON-95 study showed contrasting results, with VRD vs no consolidation, followed by lenalidomide maintenance, resulting in improved PFS in patients aged ≤65 years. 34 Lenalidomide was approved as post-ASCT maintenance therapy in 2017 35 and was not a standard of care at the time of the MMY3012 and MMY3013 studies.…”

“…22 (22) 36 (35) 0.1458 20 (26) 12 (16) 0.1445 VGPR 57 (32) 59 (33) 39 (39) 28 (27) 18 (23) 31 (40) PR 60 (34) 54 (30) 30 (30) 30 (29) 30 (38) 24 (31) MR 4 (2)…”

Response-adapted intensification with cyclophosphamide, bortezomib, and dexamethasone versus no intensification in patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial

“…Median progressionfree survival was 30 months (95% CI [25][26][27][28][29][30][31][32][33][34][35][36] in the CVD group and 20 months (15-28) in the no CVD group (HR 0·60, 95% CI 0·48-0·75, p<0·0001; figure 2A). Similar results were seen in the trans plantationeligible pathway: median progressionfree survival was 48 months (95% CI 35-not reached) in the CVD group and 28 months (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) in the no CVD group (HR 0·50, 95% CI 0·36-0·68, p<0·0001; appendix p 9); and the transplantationineligible pathway: median progression free survival was 20 months (95% CI 15-23·7) in the CVD group and 9 months (6-15) in the no CVD group (HR 0·73, 95% CI 0·52-1·02, p=0·061; appendix p 9).…”

“…In contrast to our use of induction intensification, two studies have examined the use of posttransplant consolidation. In the Stamina BMT CTN 0702 study, 23 patients were treated with initial therapy at investigators discretion followed by randomisation before autologous haemopoietic stem cell transplantation to one of three strategies: transplantation followed by lenalidomide maintenance, two autologous stem cell transplants followed by lenalidomide maintenance, or transplantation followed by posttransplant consolidation with bortezomib, lenalidomide, and dexamethasone (VRD) and then by lenalidomide maintenance. No difference in progression free survival or overall survival was identified between randomisation groups.…”

Pursuing a Curative Approach in Multiple Myeloma: A Review of New Therapeutic Strategies

“…Nevertheless, the STAMINA trial did not show any difference in PFS or OS of patients receiving double vs. single ASCT. It is always difficult to perform comparisons between different trials, but the better and prolonged induction (VRD) used in the majority of the patients enrolled in the STAMINA study (whereas 3-4 cycles of VCD were used in the EMN02 study) and the lower compliance to the second ASCT procedure reported in the same study can partially explain the different results [83].…”