High-Dose Melphalan Plus Autologous Stem Cell Transplantation as Consolidation Shows Benefit in Relapsed Multiple Myeloma After Previous Transplant
In a UK phase III trial (NCRI Myeloma X Relapse [Intensive] Trial) reported in The Lancet Oncology, Cook et al found that high-dose melphalan plus salvage autologous stem cell transplantation significantly prolonged time to progression vs cyclophosphamide in patients with relapsed multiple myeloma who had previously received autologous stem cell transplantation and were eligible for intensive therapy.
Study Details
In this open-label trial, 293 patients aged ≥ 18 years from 51 UK centers who required treatment for first progressive or relapsed disease ≥18 months after a previous autologous stem cell transplantation and who were eligible for intensive therapy received bortezomib (Velcade), doxorubicin, and dexamethasone induction therapy and underwent peripheral blood stem cell mobilization and harvesting if applicable. Between August 2008 and November 2012, 174 patients with adequate stem cell harvest were randomly assigned to receive high-dose melphalan at 200 mg/m2 plus salvage autologous stem cell transplantation (n = 89) or oral cyclophosphamide at 400 mg/m2 per week for 12 weeks (n = 85).
The stem cell transplantation and cyclophosphamide groups were balanced for age (median, 61 years in both), sex (73% and 72% male), ethnicity (91% and 94% white), isotype (IgG in 67% in both), time to progression after first stem cell transplantation (> 24 months in 72% and 75%) and cytogenetic risk (standard in 84% and 87%, adverse in 16% and 13%); International Staging System stage III disease was more common in the stem cell transplantation group (18% vs 9%).
Improved Time to Progression
After median follow-up of 31 months, median time to progression was 19 months in the salvage autologous stem cell transplantation group vs 11 months in the cyclophosphamide group (hazard ratio [HR] = 0.36, P < .0001). Median overall survival was not reached in either group (HR = 0.62, P = .19); 3-year overall survival was 80.3% vs 62.9%. Overall response was 79% after induction therapy, 83% after melphalan/stem cell transplantation, and 74% after cyclophosphamide, with stringent complete response in 8%, 39%, and 22%.
Toxicity
Among grade 3 or 4 adverse events, neutropenia (75% vs 13%), thrombocytopenia (72% vs 4%), anemia (22% vs 1%), infection (4% vs 0%), diarrhea (12% vs 1%), and nausea (8% vs 1%) were more common in the autologous stem cell transplantation/melphalan group.
The investigators concluded, “This study provides evidence for the improved efficacy of high-dose melphalan plus salvage [autologous stem cell transplantation] when compared with cyclophosphamide in patients with relapsed multiple myeloma eligible for intensive therapy, which might help to guide clinical decisions regarding the management of such patients.”
Gordon Cook, PhD, of the St. James’s Institute of Oncology, Leeds Teaching Hospitals NHS Trust, and University of Leeds, United Kingdom, is the corresponding author for the Lancet Oncology article.
The study was funded by Cancer Research UK. For full disclosures of the study authors, visit www.thelancet.com.
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