Toxicity-reduced, myeloablative allograft followed by lenalidomide maintenance as salvage therapy for refractory/relapsed myeloma patients

• Published in: Bone marrow transplantation (Basingstoke) Vol. 48; no. 3; pp. 403 - 407
• Main Authors: KRÖGER, N, ZABELINA, T, BACHER, U, BADBARAN, A, SCHILLING, G, HANSEN, T, ATANACKOVIC, D, ZANDER, A. R, KLYUCHNIKOV, E, KROPFF, M, PFLÜGER, K.-H, BURCHERT, A, STÜBIG, T, WOLSCHKE, C, AYUK, F, HILDEBRANDT, Y
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.03.2013
• Subjects: Adolescent; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - therapeutic use; Biological and medical sciences; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Care and treatment; Confidence intervals; Dexamethasone; Disease-Free Survival; Diseases; Female; Graft-versus-host reaction; Hematologic and hematopoietic diseases; Homografts; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Immunotherapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Maintenance; Male; Medical sciences; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - surgery; Multiple Myeloma - therapy; Neutropenia; Peripheral neuropathy; Recurrence; Relapse; Salvage Therapy; Statistical analysis; Stem cell transplantation; Stem Cell Transplantation - adverse effects; Stem Cell Transplantation - methods; Targeted cancer therapy; Thalidomide - adverse effects; Thalidomide - analogs & derivatives; Thalidomide - therapeutic use; Thrombocytopenia; Toxicity; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation Conditioning - adverse effects; Transplantation Conditioning - methods; Transplantation, Homologous; Young Adult; Antineoplastic agent; Relapse; myeloablative conditioning; Toxicity; Stem cell; Hematopoietic cell; Homograft; auto-SCT; Myeloma; Allogeneic hematopoietic stem cell transplantation; Immunoglobulinopathy; allo-SCT; Lymphoproliferative syndrome; Maintenance treatment; Autologous hematopoietic stem cell transplantation; Graft; Myelosuppression; Conditioning; salvage therapy; Human; Immunopathology; Treatment resistance; multiple myeloma; Hematology; Lenalidomide; B cell neoplasm; Malignant hemopathy; Lymphoid neoplasm; Immunomodulator; Salvage treatment; Cancer
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2012.142

Relapse after dose-reduced allograft in advanced myeloma patients remains high. To reduce the risk of relapse, we investigated a myeloablative toxicity-reduced allograft (aSCT) consisting of i.v. BU and CY followed by lenalidomide maintenance therapy in 33 patients with multiple myeloma (MM) who relapsed following an autograft after a median of 12 months. The cumulative incidence of non-relapse mortality at 1 year was 6% (95% confidence interval (CI): 0-14). After a median interval of 168 days following aSCT, 24 patients started with a median dose of 5 mg (r, 5-15) lenalidomide without dexamethasone. During follow-up, 13 patients discontinued lenalidomide owing to progressive disease (n=6), GvHD (n=3), thrombocytopenia (n=2), or fatigue (n=2). Major toxicities of lenalidomide were GvHD II-III (28%), viral reactivation (16%), thrombocytopenia (III-IV°,16%), neutropenia (III/IV°, 8%), peripheral neuropathy (I/II°, 16%), or other infectious complication (8%). Cumulative incidence of relapse at 3 years was 42% (95% CI: 18-66). The 3-year estimated probability of PFS and OS was 52% (95% CI: 28-76) and 79% (95% CI: 63-95), respectively. Toxicity-reduced myeloablative allograft followed by lenalidomide maintenance is feasible and effective in relapsed patients with MM, but the induction of GvHD should be considered.