Cancer Therapy Advisor: So who is most likely to benefit from allo-HSCT?
Dr Mir: Young patients with relapsed/refractory disease and poor cytogenetics/gene-expression profile who cannot be enrolled in a clinical trial, should be offered allo-HSCT as salvage therapy. They have a long-term survival of 20% in the Mayo series.
Cancer Therapy Advisor: The International Myeloma Working Group (IMWG) 2010 recommendations discourage the use of reduced-intensity conditioning (RIC) allogeneic transplantation for patients with myeloma, except in the context of clinical trials. Do you agree?
Dr Mir: Data are mixed. In the 76 transplants we looked at in the Mayo series, a myriad of conditioning regimens was found and numbers did not come to a statistical power sufficient to recommend for or against RIC. Japanese data from Kikuchi and colleagues showed a progression-free survival (PFS) of merely 5% with RIC, which is discouraging.2
Cancer Therapy Advisor: Your review of the Mayo Clinic series had 12 years’ worth of follow-up data, which is unusual. What was revealed by your team’s review of allo-HSCT outcomes at Mayo?
Dr Mir: We performed a retrospective review of 76 patients in the Mayo Clinic database from 1993 to 2013 who underwent allo-HSCT for myeloma. These were young patients (median age was 42) receiving allo-transplant as salvage therapy in more than 85% of cases, usually with myeloablative conditioning (70%).
Treatment-related mortality was 20% on day 100. PFS was 15 months, which is outstanding for any single therapy at salvage stage.
I think the most impressive finding with the availability of decades of follow-up data, was this: 20% long-term survivors at 12 years for patients undergoing allo-HSCT compared to 0 survivors in a control group.
Cancer Therapy Advisor: What factors predicted outcome for allo-HSCT recipients at Mayo? Did cytogenetics make a difference? What about donor/recipient mismatches?
Dr Mir: In multivariate analysis for PFS, number of previous treatment regimens (P = .04), overall survival, time between autologous and allogeneic HSCT was significant (P = .009).
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Cytogenetics were not available for about 50% of patients. It would have been interesting to be able to project effect of allo-transplant on high-risk disease such as 17p. Most donors were full matches. The few mismatches were not statistically significant in terms of outcome, and should not dissuade against allo. In general, though, with each mismatch, mortality increases by 10% in allo-transplants.