Allogeneic Stem Cell Transplantation (SCT) for Multiple Myeloma (MM) - What Has Changed? : A CIBMTR Analysis From 1989 – 2005.

Despite its curative potential, the role of allogeneic stem cell transplant (allo-SCT) in MM has been limited by high treatment related mortality (TRM). Autologous stem cell transplant (auto-SCT) thus remains the standard of care for eligible patients (pts) with MM. Recently interest in allo-SCT has been increasing due to the incurable nature of MM, better risk stratification models, improved supportive care and finally the increasing experience with less toxic reduced intensity conditioning. We analyzed the trends in practice of allo-SCT for MM over the past two decades. A total of 1211 pts undergoing allo-SCT for MM between 1989 and 2005, reported to the CIBMTR were analyzed in three cohorts based on year of allo-SCT: 1989–1994 (n=346), 1995–2000 (n=285), and 2001–2005 (n=580). Probabilities of progression-free survival (PFS) and overall survival (OS) and cumulative incidence estimates of TRM and relapse were calculated.

Patient characteristics are summarized in table 1. Patients transplanted in the later cohort (2001–2005) were of higher age with 53% above age 50 years (vs. 12% in 1989–1994). There was decreasing use of myeloablative regimens and bone marrow grafts over time (82% vs. 62% vs. 9% for myeloablative regimens and 99%, 62% and 13% for marrow grafts respectively). Increasing number of pts in the later cohort received an auto-SCT prior to allo-SCT (Table 1). The proportion of unrelated allo-SCTs increased over time (5% vs. 21% vs. 33%). Graft versus host (GVH) prophylaxis changed over time with increasing use of cyclosporine with agents other than methotrexate and increasing use of ATG in the recent years. Median survival increased over the three time periods from 1989 – 2005: 11.1 months (mos.) vs. 12.2 mos vs. 20.3 mos. The 100 day mortality decreased steadily over successive time periods; 35% (95% CI; 29–31), 29% (24–35) and 19% (16–23) respectively. Similarly, the TRM at 5 years remained steady between the first two periods, but decreased in the last period (40 & 48% vs. 29%). The incidence of chronic GVHD increased in the later cohort but the incidence of acute GVHD was similar over the years. While PFS was the lowest for the most recent group (15% at 5 years), the overall survival at 5 years was similar among the groups (30, 32, and 29 mos). Long term PFS at 10 years was 18% in the 1989–1994 cohort and 17% in 1995–2000. Long term OS at 10 years was 23% in 1989 – 1994 and 1995–2000 cohorts. Results are summarized in table 1. A clear trend towards reduced intensity conditioning, unrelated donor SCT, use of PBSC grafts and selection of older patients was noted. There was increasing use of tandem auto-allo SCT with an increasing proportion of patients with a prior auto-SCT. While the TRM has decreased significantly in the last cohort, this did not translate into an improvement in survival primarily because of increased risk of relapse in the latter cohort. Long term (>10yr) progression free survival which may approach a cure has remained unchanged over the past two decades at <20%.

Lonial:Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.