Outcomes of Salvage Autologous Versus Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma Relapsed After Initial Autologous Hematopoietic Cell Transplantation

ABSTRACT

BACKGROUND: Standard therapy for multiple myeloma (MM) includes initial autologous hematopoietic cell transplantation (autoHCT1) but this is not curative and most patients will relapse. Data on salvage autoHCT2 or allogeneic HCT (alloHCT2) are limited and the optimal salvage strategy is unknown.

METHODS: This is a retrospective study of MM patients >18 years of age who relapsed after  autoHCT1 and underwent salvage autoHCT2 or alloHCT2 between 1995-2011 at our institution. Tandem auto-autoHCT or auto-alloHCT were excluded. 

RESULTS: Characteristics of autoHCT2 (N=27) and alloHCT2 (N=19) patients were not significantly different except the alloHCT2 median age was significantly (p = 0.002) lower (54 years) than for autoHCT2  (62 years) and  more alloHCT2 patients had KPS ≥ 70%  (p=.031). Complete and very good partial remission (CR/VGPR) improved from 7% to 56% after autoHCT2  and from 26% to 37% after alloHCT2.  Of 15 patients with progressive disease (PD) at the time of  autoHCT2, 5 achieved CR/VGPR and 7 PR.  Nonrelapse mortality (NRM) at 3 years was 3.7% for autoHCT2 and 5.3% for alloHCT2 (p=.901). Median progression free survival (PFS) and overall survival (OS) for autoHCT2 (19 months, 23 months) and alloHCT2 (6 months, 19 months) were not significantly different. For those entering salvage autoHCT2 in PD, PFS at 3-years was 41.7% (15.2-68.1%) and OS at 3-years was 45% (16.1-73.9%). On multivariate analysis, time from autoHCT1 to relapse <1year vs. ≥1year (HR  24.81 [95% CI 2.4-249.9]) and no maintenance therapy vs. given after autoHCT2 (HR 12.19 [95% CI 2.5-249.9]  impacted OS after autoHCT2. However, only time from autoHCT1 to relapse <1 year versus ≥1 year (HR 18.55 [95% CI 2.28-150.57]) impacted PFS after autoHCT2. For  alloHCT2, no factors impacted NRM, PFS or OS.  For those with relapse from autoHCT1 <1 year versus ≥1 year undergoing autoHCT2, median OS was 15 months (1-53) vs. not yet reached at 143 months and median PFS was 5 months (1-49) vs.  not yet reached at 88 months.  Major causes of death for alloHCT2  were PD (n= 5), GVHD (n=3), while for  autoHCT2, PD (n=10), infection (n=3).

CONCLUSIONS: Salvage autoHCT2 and alloHCT2 are both feasible for patients with post autoHCT1 MM relapse.  Relpase ≥ 1 year from autoHCT1 predicts for better PFS and OS in the autoHCT2 group. Those with progressive disease can also be salvaged by autoHCT2.  Maintenance therapy after autoHCT2 is beneficial and should routinely be used.