Similar Outcome with Early Reduced Intensity Conditioning (RIC) Allogeneic Transplant to Autologous-Non-Myeloablative Allogeneic (Auto-Allo) Transplant in Patients with Multiple Myeloma.
Authors: Firoozeh Sahebi , Schriber Jeffery R. , Spielberger Ricardo , Cai Ji-Lian , Kogut Neil Martin , Falk Peter M. , Parker Pablo Miguel , Krishnan Amrita , Popplewell Leslie , Karanes Chatchada , Qian Dajun , Forman Stephen J. , Somlo George 
Published: October 2019

Although autologous transplant remains standard of care for patients with multiple myeloma, it is rarely curative. Allogeneic peripheral stem cell transplant (PSCT) using reduced intensity conditioning (RIC) or non-myeloablative conditioning following autologous PSCT (auto-allo) have been used in an attempt to improve survival. Although the graft vs. myeloma effect is an important therapeutic aspect of these approaches higher relapse rates have been reported using reduced intensity regimens suggesting that cytoreduction with auto PSCT (auto-allo) is required for optimal disease control. To examine the differences between RIC and auto-allo PSCT we performed a retrospective analysis of 49 patients who underwent auto-allo and RIC transplants. Thirty-seven patients received an auto-allo PSCT using melphalan (200mg/m2) prior to auto PSCT and TBI (200 cGy) prior to allograft PSCT and twelve patients underwent RIC allograft PSCT following fludarabine (125mg/m2) and melphalan (140mg/m2), between Feb 2000 to April 2005. Donors included HLA matched siblings (47) or matched unrelated donors (2 in the RIC group). Median follow up for the alive patients is 4.5 and 5.4 years for the auto-allo and the RIC groups, respectively. Median age was 51 years in the auto-allo group (range 38–66) and 48 years in the RIC group (range 42–62). Patients in the auto-allo group received their allograft within 60–120 days following autologous PSCT. In the RIC group, 7 patients failed a previous single (1) or tandem (6) auto PSCT. Cytogenetic data were available in 47 patients prior to transplant, with chromosome 13 deletion present in 2 patients in the auto-allo group and in 4 patients in the RIC group. Median B2-microglobulin was 1.8 in the auto-allo group and 2.1 in the RIC group. There were more patients in complete remission (CR)/partial remission (PR) in the auto-allo group (76%) than in the RIC group (17%, P= 0.0005), and there were more patients who received early transplant (< one yr) in the auto-allo group (68%) than the RIC group (8%, P= 0.0005). There was no difference in 1 year non-relapse mortality between the two groups (5% auto-allo vs. 8% RIC, P=1.00. Three year overall survival (OS) was statistically superior in the auto-allo group (81%) versus the RIC group (35%, P=0.02). Three year PFS was 54% in the auto-allo group and 21% in the RIC groups (P=0.11). However, when Cox regression analysis was performed adjusting for the disease status and time from diagnosis, there was no statistically difference in the OS between the 2 groups (P=0.27).

Conclusion: Our data suggest that RIC allograft and auto-allo PSCT-associated treatment related mortality is similar, and RIC allograft when administered earlier during the disease course may result in similar outcome. However whether using early reduced intensity allogeneic transplant could eliminate the need for cytoreductive auto-PSCT needs to be addressed in prospective clinical trial.