...A subset of patients may have been cured with an allograft...

For the treatment of young patients with myeloma, autologous transplantation has been regarded the standard of care. While the introduction of newer agents, such as lenalidomide and bortezomib, have dramatically changed the treatment landscape for this disease, allografting is still considered the only means of a cure. The high transplant-related mortality associated with this procedure, however, limits its use. Reduced-intensity regimens and improved non-myeloablative allografting techniques have resulted in lower rates of relapse and provided promising results. However, whether non-myeloablative allografting improves survival compared with autografting has been a long-debated issue.

To address this issue, Luisa Giaccone and collaborators designed a trial to assess the outcomes after either a cytoreductive autograft followed by non-myeloablative allograft or a second melphalan-based autograft in myeloma patients. Treatment was assigned based on the presence or absence of HLA-identical siblings, and the long-term outcomes reported. Patients without an HLA-identical sibling received double autologous transplantation. The primary end points of the trial were overall survival and event-free survival (EFS).

The overall response rates did not differ significantly between the groups, but the complete remission rate was significantly higher after non-myeloablative allograft compared with the second autograft. At a median follow up of 7.1 years, the median overall survival and EFS were significantly longer in patients treated with allografting. The median overall survival was not reached in allograft-treated patients; EFS was 39 months. The corresponding values in patients treated with two autografts were 5.3 years and 33 months.

Since the combination of newer drugs with allografting has not been extensively explored, the researchers comment that “the combination of allografting with new drugs should most preferably be explored in high-risk patients, where life expectancy is poor, in prospective clinical trials”. Giaccone's team conclude “a subset of patients may have been cured with an allograft given the persistent disease-free status extending beyond 10 years.”