High-dose melphalan chemotherapy plus salvage autologous stem cell transplantation in patients with relapsed multiple myeloma significantly prolonged time to progression compared with conventional low-dose cyclophosphamide, according to results of a randomized, open-label, phase 3 trial.
No standard treatment exists for relapsed myeloma, and the role of autologous stem cell transplantation in this patient population is not clear, according to background information provided by researchers.
Gordon Cook, MB, ChB, PhD, consultant hematologist and myeloma lead at St. James Institute of Oncology in the United Kingdom, and colleagues compared high-dose melphalan (Alkeran, GlaxoSmithKline) plus salvage ASCT with cyclophosphamide in patients with first progressive or relapsed multiple myeloma. All patients had undergone previous ASCT, and at least 18 months elapsed since their previous transplant.
Prior to study randomization, 293 patients underwent induction therapy with bortezomib (Velcade, Millennium), doxorubicin and dexamethasone, followed by peripheral blood stem-cell mobilization and harvesting, if appropriate.
The 174 patients with sufficient peripheral blood stem cells were randomly assigned to 200 mg/m2 high-dose melphalan plus salvage ASCT (n=89) or 400 mg/m2 oral cyclophosphamide weekly for up to 12 weeks (n=85).
Disease progression served as the primary endpoint. Median follow-up was 10.1 months.
Cook and colleagues reported significantly longer median time to progression (19 months vs. 11 months; HR=0.36; 95% CI, 0.25-0.53) among patients assigned melphalan plus salvage ASCT.
Philip L. McCarthy
At the time of data cut-off, median OS had not been reached in either arm but researchers did not observe significant differences. Rates of 3-year OS were 80.3% (95% CI, 69.3–91.2) for the salvage ASCT group and 62.9% (95% CI, 46.6–79.2) for the cyclophosphamide group.
The most commonly reported grade 3 to grade 4 adverse events following induction therapy were thrombocytopenia (51%), neutropenia (43%) and peripheral neuropathy (12%). After randomization, researchers reported higher rates of neutropenia (76% vs. 13%) and thrombocytopenia (72% vs. 5%) in the salvage ASCT group.
“Salvage ASCT can now be considered a standard treatment after re-induction therapy for eligible patients with multiple myeloma relapsing after first ASCT, especially beyond 12 months to 18 months after first relapse,” Philip L. McCarthy, MD, of the adult blood and marrow transplant program at Roswell Park Cancer Institute, wrote in an accompanying editorial. “New therapies directed against other multiple myeloma intracellular pathways and antibodies that target cell surface antigens might serve as experimental comparisons to salvage transplant after disease progression.”
For more information:
- Cook J. Lancet Oncol. 2014;doi:10.1016/S1470-2045(14)70245-1.
- McCarthy PL. Lancet Oncol. 2014;doi:10.1016/S1470-2045(14)70279-7.
Disclosure: The study was funded by Cancer Research UK. The researchers report honoraria, research funding and speakers bureau fees from Janssen. McCarthy reports advisory board roles with Celgene, Janssen, Millennium, Sanofi and Takeda.