Bortezomib for post-allogeneic hematopoietic stem transplantation relapse and GVHD in multiple myeloma: a single institute experience

Abstract

Allogeneic hematopoietic stem cell transplantation (alloSCT) can result in remission and long-term survival for multiple myeloma (MM), but its effect has been often hampered by high rates of therapy-related death by graftversus-host diseases (GVHD), disease progression, or infection [1]. We retrospectively investigated the efficacy and safety of Bortezomib (Bor) alone or with dexamethasone (Dex) (BD) for MM patients with disease progression following allo-SCT. Six MM patients were treated with Bor alone or with BD as the salvage treatment for disease progression following allo-SCT, while 32 patients with relapsed/refractory MM without allo-SCT were also treated with BD at our institute between October 2003 and July 2009. The median age was 39.5 years old for the allo-SCT cohort and 67.5 for the non-allo-SCT cohort. None had prior exposure to Bor. In six post-allo-SCT patients, two underwent a conditioning regimen with high-dose cyclophosphamide (60 mg/kg) plus total body irradiation (10 Gy), while four were treated with a reduced intensity-conditioning regimen using fludarabine (90–125 mg/m) plus melphalan (140–200 mg/m) (Table 1). According to the International Myeloma Working Group response criteria, the best response for alloSCT was complete remission (CR) in one, very good partial response (VGPR) in two and stable disease (SD) in three patients. Bor (1.3, 1.0, or 0.7 mg/m/day) was administered on days 1, 4, 8 and 11, and Dex on days 1, 2, 4, 5, 8, 9, 11 and 12, every 21 days. The dosage of either agent was adjusted by the attending physician in the light of the patient’s condition. Among the six post-allo-SCT patients, one received Bor alone and five received BD, while all patients in the non-allo-SCT cohort received BD. The median number of cycles of Bor alone or BD was 3 (1–7 cycles) for the post-allo-SCT cohort and 2 for the non-allo-SCT cohort. The median interval between allo-SCT to Bor or BD was 12.5 months (6–22 months). All presented acute and chronic GVHD. Three patients received thalidomidecontaining therapy for post-allo-SCT disease progression prior to Bor (Table 2). For the six post-allo-SCT patients, the overall response rate (ORR) was 50.0%, including two VGPR and one PR, while two died of MM progression and one of bacterial pneumonia complicated with bronchiolitis obliterans, a late complication of allo-SCT. Although ORR for the allo-SCT cohort was inferior to that of the non-alloSCT cohort (68.8%), the median overall survival (OS) (912 days) and median progression-free survival (PFS) (71 days), 2-year OS (66.7%) and 2-year PFS (33.3%) from the start of Bor-containing treatment for the allo-SCT cohort did not seem significantly different from those for the non-allo-SCT cohort, although the statistical analysis was not applicable due to the small number of patients (Supplementary Fig. 1). Our findings thus seem to provide further supportive evidence that Bor or BD constitutes a promising salvage treatment even for heavily treated Electronic supplementary material The online version of this article (doi:10.1007/s12185-010-0709-3) contains supplementary material, which is available to authorized users.