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Partially T-Cell–Depleted Allogeneic Stem-Cell Transplantation for First-Line Treatment of Multiple Myeloma: A Prospective Evaluation of Patients Treated in the Phase III Study HOVON 24 MM

Henk M. Lokhorst, Christine M. Segeren, Leo F. Verdonck, Bronno van der Holt, Reinier Raymakers, Marinus H.J. van Oers, Renee M.Y. Barge, Harry C. Schouten, Petra H.M. Westveer, Monique M.C. Steijaert, Jan J. Cornelissen, Pieter Sonneveld for the Dutch-Belgian Hemato-Oncology Cooperative Group

From the Department of Hematology, University Medical Center Utrecht, Utrecht; Department of Hematology and HOVON Data Center, Erasmus Medical Center, Rotterdam; Department of Hematology, University Medical Center Nijmegen, Nijmegen; Department of Hematology, Academic Medical Center, Amsterdam; Department of Hematology, Leiden University Medical Center, Leiden; and Department of Hematology, Academic Medical Center, Maastricht, the Netherlands.

Address reprint requests to H.M. Lokhorst, MD, PhD, Department of Hematology, University Medical Center Utrecht, HP G03.647, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; email: H.Lokhorst{at}azu.nl.

Purpose: To determine in a prospective study the efficacy, toxicity, and long-term outcome of up-front allogeneic stem-cell transplantation (allo-SCT) in multiple myeloma (MM).

Patients and Methods: In the prospective phase III study by the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), HOVON 24 MM, 53 patients with an HLA-identical sibling (median age at transplantation, 48 years; range, 31 to 56 years) were allocated to a partial T-cell–depleted allo-SCT after induction therapy.

Results: The overall response rate after allo-SCT was 89% (47 of 53 patients), including the 19% of patients (10 of 53 patients) with a complete remission (CR). Five patients achieved a CR only after allo-SCT. Five (71%) of seven primary refractory patients obtained a response to allo-SCT, all of whom had a partial remission. With a median follow-up of 38 months (range, 25 to 61 months), 20 patients are alive since allo-SCT and 33 patients have died (14 from progressive disease, 18 from treatment-related mortality [TRM], and one from another cause). Occurrence of acute graft-versus-host disease grades 2 to 4 predicted for higher TRM in a time-dependent analysis. The median progression-free survival time after allo-SCT was 17 months. Median overall survival time after allo-SCT was 25 months, or 29 months from the start of therapy. Only three patients are in continuing CR, indicating that the potential cure rate of this approach is, at best, 6%.

Conclusion: This first prospective evaluation of up-front allo-SCT of MM in a multicenter setting does not support the use of T-cell–depleted myeloablative allo-SCT as part of first-line therapy.

Supported by grant no. Ontwikkelingsgeneeskunde OG 96-020 from the Dutch Ministry of Health.

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