Researchers found that double vs single autologous stem cell transplantation (ASCT) improved survival in patients with newly diagnosed multiple myeloma, according to results of a study (abstract 124) presented at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 1–4 in San Diego.
Results from two recent randomized trials comparing a single ASCT (ASCT-1) vs a double ASCT (ASCT-2) were mixed. The investigators, led by Michele Cavo, MD, of Bologna University School of Medicine in Bologna, Italy, hypothesized that these conflicting results were due to variations in trial design, and performed a long-term follow-up analysis of patient-level data from three clinical trials of bortezomib-thalidomide-dexamethasone (VTD) or bortezomib-doxorubicin-dexamethasone (PAD). This induction therapy before ASCT was then followed by post-ASCT bortezomib-based consolidation and/or maintenance treatment.
The analysis included 909 patients (median age, 58 years) who were randomized to VTD or PAD study arms, with assignation to either ASCT-1 (n = 501) or ASCT-2 (n = 408) planned at study entry. In the VTD and PAD groups, the rates of Multiple Myeloma International Staging System (ISS) stage III were 20% and 17%, respectively.
During a median follow-up period of 117 months, the researchers found that patients receiving ASCT-2 vs ASCT-1 demonstrated longer progression-free survival (PFS) (median, 47 vs 38 months; hazard ratio [HR], 0.76; 95% CI, 0.65–0.89; P = .0008) and longer overall survival (OS; estimated 10-year probability, 58% vs 47%; HR, 0.69; 95% CI, 0.56–0.84; P = .0002). Furthermore, the PFS benefit with ASCT-2 was sustained across prespecified subgroups, including patients with standard- or high-risk cytogenetics.
In those patients with standard-risk cytogenetics, the 10-year OS rates were 72% for ASCT-2 vs 60% for ASCT-1 (HR, 0.68; 95% CI, 0.52–0.88; P = .004). In those with high-risk cytogenetics, these rates were 51% for ASCT-2 vs 34% for ASCT-1 (HR, 0.54; 95% CI, 0.36–0.83; P = .004).
“Results of this pooled analysis of phase III studies incorporating bortezomib-based triplets into ASCT confirmed the superiority of ASCT-2 over ASCT-1 in terms of extended PFS and OS,” concluded the researchers. “The subgroup of patients at high risk mostly benefited from ASCT-2, in particular those who had advanced ISS stage, adverse cytogenetics, and failed to achieve complete response.”
In an interview with Cancer Network, Ceri Bygrave, MD, MPhil, a consultant hematologist at the University Hospital of Wales, reflected on this study. “This study further cemented the idea that tandem transplant can benefit high-risk patients,” she said. “[Dr. Cavo and colleagues] picked out patients with high-risk cytogenetics and ISS stage II and III disease and showed a significant improvement in PFS and OS for this group, which justifies ongoing use of tandem in certain populations."