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Allogeneic vs. Second Autologous Stem-Cell Transplantation for Newly Diagnosed Myeloma

These results build on previous reports of better outcomes with sequential allogeneic or autologous SCT than with single transplants.

Autologous stem-cell transplantation (SCT) is the standard therapeutic approach for younger patients with multiple myeloma (MM), because it often lengthens duration of response and survival (N Engl J Med 2003; 348:1875). However, virtually all patients ultimately relapse following this procedure, so a variety of therapeutic strategies are being evaluated to lengthen survival further and to achieve a cure. One promising alternative is second SCTs (autologous or allogeneic) during remission (N Engl J Med 2003; 349:2495 and J Clin Oncol 2004; 22:1674).

Investigators in Italy and Washington treated 162 consecutive patients (age, 65) with newly diagnosed MM. All patients received VAD (vincristine, doxorubicin, dexamethasone) induction chemotherapy followed by stem-cell mobilization, melphalan conditioning therapy, and autologous SCT. Sixty patients with HLA-matched siblings then were scheduled for allogeneic SCTs (autoallo group), whereas 82 without matched siblings (as well as 20 who refused allogeneic transplant or whose donors were ineligible) were scheduled for second autologous SCTs (autoauto group). The conditioning regimens differed between the arms: Autoallo patients received melphalan (200 mg/m²) before their autologous SCTs and then nonmyeloablative doses of total-body irradiation prior to their allogeneic SCTs, whereas autoauto patients received melphalan before each transplant.

Complete remission rates were higher in the autoallo group than in the autoauto group (55% vs. 26%; P=0.004). Median event-free and overall survival were significantly longer in patients with matched siblings (even though this analysis included all patients with matched siblings, regardless of whether they actually received allogeneic transplants). Treatment-related mortality rates did not differ between the study arms, but significantly more patients died of MM in the autoauto group than in the autoallo group (43% vs. 7%). About two thirds of the autoallo group developed graft-versus-host disease (GVHD); a 32% cumulative 2-year incidence of extensive chronic GVHD was reported.

Comment: The clinical management of MM has evolved rapidly in recent years with the advent of new therapeutic approaches, including thalidomide or lenalidomide with pulsed corticosteroids, bortezomib, and dose-intensive therapy followed by SCT. Bisphosphonates have lowered the previously considerable morbidity related to skeletal complications, albeit with recently recognized osteonecrosis complications in some patients. Results from the current study build on previous reports of better outcomes with sequential allogeneic or autologous SCT than with single transplants, and the data suggest that a graft-versus-myeloma effect occurs with allogeneic SCT. The differences in conditioning regimens between the two arms of this study limit the conclusions that can be drawn, however. Furthermore, better outcomes might be achieved with either transplant approach — or even with delayed or deferred transplant — if more-effective initial therapy that incorporates immunomodulatory agents or proteosome inhibitors is used. Algorithms for MM management continue to evolve, and discussions with newly diagnosed patients should include the role and timing of SCT, as well as participation in one of several ongoing clinical trials.

— Michael E. Williams, MD

Published in Journal Watch Oncology and Hematology March 14, 2007

Citation(s):

Bruno B et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 2007 Mar 15; 356:1110-20.

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