Allogeneic stem cell transplantation and subsequent treatments as a comprehensive strategy for long-term survival of multiple myeloma patients

Abstract

We evaluated 71 patients treated with allogeneic hematopoietic cell transplantation (allo-HCT) for multiple myeloma (MM). Forty-three patients (61%) received allo-HCT after the first line of therapy. Fifty-eight patients (82%) had chemosensitive disease at the time of allo-HCT. A HLA-matched related or unrelated donor was available for 68 patients (96%). Non-myeloablative or reduced-intensity conditioning regimen and peripheral blood hematopoietic cells as a graft source were used in most patients. The cumulative incidence of grade II-IV acute GVHD at day +100 and chronic GVHD at 5 years was 13% (95% CI 7-23%) and 35% (95% CI 24-46), respectively. Non-relapse mortality and relapse/progression incidence at 5 years were 12% (95% CI 5-23) and 65% (95% CI 49-76), respectively. With a median follow-up in survivors of 100 months (range 16-186), the 5-year PFS and OS were 39% (95% CI 27-52) and 60% (95% CI 55-77), respectively. On multivariate analysis: age >55 years was associated with both a reduced PFS (RR 2.11, 95% CI 1.15-3.87) and OS (RR 5.53, 95% CI 2.22-13.76); chemorefractory disease at allo-HCT was associated with both reduced PFS (RR 3.09, 95% CI 1.37-7.00) and OS (RR 3.19, 95% CI 1.23-8.22). At relapse, 24 patients (56%) received bortezomib, 28 (65%) lenalidomide, 11 (26%) pomalidomide, 16 (37%) donor lymphocytes infusion as part of salvage therapy after allo-HCT relapse. Median PFS from time of salvage treatment was 7 months (range 0-113 months) for bortezomib-based therapy, 14 months (range 0-79 months) for lenalidomide and 10 months (range 1-28) for pomalidomide. Allo-HCT is a feasible and effective strategy in selected patients with MM and could be an effective platform for subsequent therapies.

Presalvage International Staging System Stage and Other Important Outcome Associations in CD34+-Selected Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma

“…Our results are comparable to those reported in an Italian cohort of 71 RRMM patients undergoing conventional alloHCT with in vivo T cell depletion and post-transplantation immune suppression, which reported a median PFS of 24 months, a median OS not met, and a 5-year OS of 60% [13]. Substantial interstudy heterogeneity limits meaningful direct comparison, but we note that our cohort was higher risk in all reported variables, including baseline ISS stage, HCT-CI, pre-alloHCT treatment lines, proportion of mismatches, use of myeloablative conditioning, and time from diagnosis to alloHCT [13]. Taken together, these results reinforce that alloHCT offers potential for long-term OS and PFS in high-risk refractory MM patients.…”

“…Older age (55 years) was also strongly associated with poorer PFS and OS, with estimated decreases of 21% and 35%, respectively, at 3 years. This has been demonstrated previously in this and other nontransplantation RRMM cohorts [1,3,12,13], which may suggest that age-specific factors that drive adverse outcomes in the nontransplantation population have similar and transplantation-independent impacts in alloHCT recipients. This possibility is reinforced by the lack of association of age with NRM in our cohort and the overall low rates of NRM and GVHD that we observed.…”

“…Similar to our previous report, CD34 + -selected alloHCT in this high-risk RRMM cohort achieved prolonged PFS and OS (median, 14 and 40 months, respectively), both of which are substantially better than rates reported in similar cohorts of high-risk RRMM patients treated with nontransplantation strategies (median PFS of 5 months and OS of 9 to 13 months) [1,3,12]. Our results are comparable to those reported in an Italian cohort of 71 RRMM patients undergoing conventional alloHCT with in vivo T cell depletion and post-transplantation immune suppression, which reported a median PFS of 24 months, a median OS not met, and a 5-year OS of 60% [13]. Substantial interstudy heterogeneity limits meaningful direct comparison, but we note that our cohort was higher risk in all reported variables, including baseline ISS stage, HCT-CI, pre-alloHCT treatment lines, proportion of mismatches, use of myeloablative conditioning, and time from diagnosis to alloHCT [13].…”

Conditioning‐based outcomes after allogeneic transplantation for myeloma following a prior autologous transplant (1991‐2012) on behalf of EBMT CMWP

“…At a median follow‐up of 12.3 years from alloHCT and 12.1 years after tandem autoHCT, median overall survival (OS) was 11.4 years in the alloHCT arm and 3.9 years in the autoHCT arm ( P = .007). In the light of these and similar reports, AlloHCT in myeloma is increasingly being seen as a platform for subsequent immunotherapeutic strategies …”

“…The initial superior OS seen in the Auto-Allo group that lessens over time may at least in part be due to the fact that the group is defined based on the administration of an allogeneic transplant after the au- AlloHCT in myeloma is increasingly being seen as a platform for subsequent immunotherapeutic strategies. 1,[28][29][30][31] In summary, these four different approaches to conditioning in patients with myeloma who had relapsed following a prior autoHCT yielded comparable engraftment, response rates and a similar incidence of chronic GvHD though the NMA group had less acute GvHD.…”