As explained in the report in the Journal of Clinical Oncology online July 4, high-dose chemotherapy (HDT) with autologous stem-cell transplantation is the gold standard in treating multiple myeloma patients up to age 65. On the other hand, allogeneic stem-cell transplantation with myeloablative conditioning may reduce relapse rates but is associated with severe toxicity; however, reduced-intensity conditioning regimens have decreased toxicity and treatment-related mortality.
Direct comparison studies of the two approaches have yielded differing results, Dr. Bo Bjorkstrand at the Karolinska Institute in Stockholm, Sweden, and colleagues point out. They therefore conducted a prospective study in which previously untreated multiple myeloma patients received treatment with HDT and autologous stem-cell transplantation followed by reduced-intensity conditioning with allogenic stem-cell transplantation, or autologous transplantation alone, based on the availability of an HLA-identical sibling donor.
The study included 108 patients in the autologous-allogeneic group and 249 in the autologous-only group. At 60 months, on intention-to-treat analysis, actuarial progression-free survival was significantly better in the autologous-allogeneic arm (35%) than the autologous-only arm (18%; p=0.001), the team reports.
Corresponding overall survival rates were 65% versus 58% (p=0.006), according to the report.
Mortality not related to relapse at 24 months was “reasonable” in both groups at 12% in the autologous-allogeneic arm and 3% in the autologous-only arm, the investigators found. Among patients who received reduced intensity conditioning and allogeneic transplants, the incidence of grade 2-4 acute graft-versus-host disease (GvHD) was 20%, and the incidence of limited and extensive chronic GvHD was 31% and 23%.
Dr. Bjorkstrand and colleagues point out that survival curves drop continuously after autologous transplantation alone, but they level off over time following the allogeneic transplantation procedure. They comment, “The possibility that a fair number of patients might be cured can justify the treatment-related mortality and GvHD morbidity.”
The investigators conclude, “We suggest that all patients who are eligible for HDT and have an HLA-identical sibling should be considered as candidates for (reduced-intensity conditioning and allogeneic stem-cell transplantation) as part of first-line treatment.”