Improved Outcome of Allogeneic Transplantation in High-Risk Multiple Myeloma Patients After Nonmyeloablative Conditioning

Abstract

PURPOSE: We present our experience with relapsed and recently diagnosed patients with high-risk multiple myeloma (MM) receiving immunosuppressive, nonmyeloablative melphalan (MEL)-based conditioning regimens (mini-allograft). PATIENTS AND METHODS: Thirty-one MM patients received allografts from HLA-matched siblings (n = 25) or unrelated donors (n = 6) using a mini-allograft. Seventeen had progressive disease (PD) and 14 had responsive disease (RD) (six with primary RD and eight with responsive relapse). Thirty patients had received one (n = 13) or two or more (n = 17) prior autologous transplantations (ATs). Median age was 56 years (range, 38 to 69 years). Twenty-one patients had chromosome 13 abnormality. Two patients were hemodialysis dependent. Blood and bone marrow grafts were administered to 28 and three patients, respectively. Donor lymphocyte infusions were given to 18 patients either to attain full donor chimerism (n = 6) or to eradicate residual disease (n = 12). RESULTS: By day 100, 25 (89%) of 28 patients were full donor chimeras, one was a mixed chimera, and two had autologous reconstitution. Acute graft-versus-host disease (GVHD) developed in 18 patients (58%), and 10 progressed to chronic GVHD (limited in six and extensive in four). At a median follow-up of 6 months, 19 (61%) of 31 patients achieved complete/near complete remission. Twelve patients (39%) have died: three of PD, three of early treatment-related mortality (TRM) (before day 100), and six of late TRM. Median overall survival (OS) was 15 months. At 1 year, there was a significantly longer event-free survival (86% v 31%, P =.01) and OS (86% v 48%, P =.04) when a mini-allograft was performed after one versus two or more prior ATs, respectively. When compared with historical MM controls (n = 93) receiving conventional allografts, early TRM was significantly lower (10% v 29%, P =.03), and OS at 1 year was better (71% v 45%; P =.08) in the mini-allograft MM patients. CONCLUSION: Mini-allograft induced excellent disease control in MM patients with high-risk disease, but is still associated with a significant GVHD.