Timing of Allogeneic Hematopoietic Cell Transplantation for High Risk Multiple Myeloma

Introduction: Despite remarkable progress, a majority of patients with multiple myeloma (MM) relapse with curability limited. Allogeneic stem cell transplantation (Allo-SCT) remains a potentially curative option for these patients with a well described but modest graft-versus-myeloma effect. We report here long term follow-up of our single institution experience with Allo-SCT in MM with a focus on evaluation of timing of Allo-SCT. Methods: We retrospectively evaluated all related/unrelated HLA-matched patients who underwent Allo-SCT between January 2000 and December 2010. Inclusion criteria included age 18 years or older and first allogeneic transplant. Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus and mini-methotrexate. Disease risk was defined by the international staging system and Co-Morbidity Index by Sorror et al. (HCT-CI). High risk cytogenetics included deletion 13q, 1q, or 17p as well as translocation 4;14 or 14;16. Results: A total of 35 patients met inclusion criteria. Median follow up was 6.6 years. Donor source was mostly Allo-Sib (74%) and conditioning mixed (44% myeloablative). 8(22%) underwent primary Allo-SCT after induction, 15(43%) planned tandem autologous transplantation (Auto-SCT) followed by Allo-SCT, and 12(34%) Allo-SCT as late salvage after failed Auto-SCT. In this high risk or heavily pre-treated patient population, all 34 patients were ISS stage III, 8(24%) had high risk cytogenetics, and the median number of prior regimens was 4. Most patients had low (47%) or intermediate (38%) HCT-CI. Median relapse free survival (RFS) was 47.2 months and median overall survival (OS) 58.9 months (Figure 1). Univariate time to relapse as a function of demographics and clinical outcomes (including acute and chronic GVHD, regimen intensity, pre and post-transplant status, donor type) demonstrated no factors predictive of relapse. In contrast, for overall survival (OS) acute GVHD grade III-IV was strongly predictive of better survival with a hazard ratio of 3.49 (P = .03). One year transplant related mortality (TRM) was 13.7% for the entire cohort. In multivariable model, acute GHVD III-IV was again predictive of OS with a hazard ratio of 3.97 (P = .02). We found no difference in OS between planned tandem Auto-SCT/Allo-SCT versus up front Allo-SCT alone. In addition a small cohort (20%) in the salvage Allo-SCT group achieved long term survival up to 10 years (Figure 2).Figure 2OS by Transplant Approach.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusion: We found no difference in outcome for high risk patients undergoing first Allo-SCT with or without planned Auto-SCT first, supporting the strategy being tested in the current BMT-CTN trail (1302). In addition there continues to be a role for salvage allograft in the modern era. We did not find an obvious benefit to chronic GVHD in these patients, a finding that will need to be verified in larger cohorts.