Impact of Pre-Transplant Depth of Response on Outcomes in Patients with Multiple Myeloma: A Report on Behalf of Pakistan Blood and Marrow Transplant Group

Background: Newly diagnosed transplant eligible multiple myeloma (MM) patients, receive treatment prior to autologous stem cell transplant (ASCT) transplant for a finite period. Retrospective studies have shown improved progression free survival with deeper pre-ASCT responses. Our objective was to analyze the impact of pre-transplant depth of response on outcomes in MM patients. Subjects and methods: This retrospective multicentre study was done on behalf of plasma cell disorders working party of Pakistan Blood and Marrow Transplant (PBMT) group. The study included 223 patients receiving ASCT between January 2005-December 2023 from 6 centers (both public and private). Pre-transplant responses were documented as per the International Myeloma Working Group criteria. Summary statistics were used to describe the population. Kaplan-Meier methodology estimated DFS and OS, log rank test was used to compare the outcomes as per response status prior to transplant. Results:The mean age was 48.78 ± 9.5 years (range: 21 - 72 years). There were 157 (70.4%) males and 64 (28.7%) females. Backache was present in 56% and 15% presented with pathological fractures. Laboratory parameters showed anemia in 45% and azotemia in 26% of patients. The most common paraprotein was IgG kappa (31%). By the international staging system (ISS), 33.3% were stage 1, 27.4% were stage II and 37.6% were stage III. First line chemotherapy was Bortezomib, lenalidomide, dexamethasone (RVd) in 42% and Bortezomib, cyclophosphamide, dexamethasone (CyBorD) in 41% of patients. Stringent complete remission (sCR) was seen in 7.4%, CR in 22%, VGPR in 19% and PR in 18% after first line chemotherapy. Second line regimens were used in used in 78 (35%) patients due to inadequate response to first line treatment. Carfilzomib based triplet was most used regimen in 54 (69.2%) patients. Complete remission (CR) was seen in 25% and very good partial response (VGPR) in 35% after salvage treatment. On univariate analysis younger age (<50 years), response to first line induction, pre- transplant responses better than VGPR were statistically significant (p=<.05). While on multivariate analysis, response of CR or better was associated with superior OS (p=.007 95% CI .215-.781) and DFS (p=.001 95% CI 0.245 - 0.712) At the time of transplant, 131 (58.3%) patients were in sCR/CR, 45 (20.2%) in VGPR, 44 (19.7%) in partial response (PR) and 2 patients (1%) had stable disease (SD). Overall survival (OS) was 72.4% at a median of 72 months (95% CI 62.8 - 82.1) while disease free survival (DFS) was 57.1% at median 47 months (95% CI 36.2 - 59.3). Both OS (82.2% versus 57.7%, p=0.001) and DFS (70.1% vs 38%, p=0.000) was significantly better in patients achieving sCR/CR pre-ASCT versus VGPR or less. Conclusion: Pre-transplant depth of response affects outcomes of MM patients receiving ASCT in resource limited settings lacking access to daratumumab, bispecific and chimeric antigen receptor T-cell therapies. Deeper responses are preferred to improve OS and DFS of transplant eligible patients.