Real World Outcomes of Autologous Stem Cell Transplant in Multiple Myeloma: A Study on Behalf of Plasma Cell Dyscrasia Working Party of Pakistan Blood and Marrow Transplant Group

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Introduction Early autologous stem cell transplant (ASCT) is recommended for transplant eligible multiple myeloma (MM) patients. However, there is a limited data on outcomes of ASCT in patients from low middle income countries (LMIC). Objective To report real world outcomes of ASCT in MM patients from a resource constraint country. Methods This multicenter, retrospective observational study was done on behalf of Pakistan Blood and Marrow Transplant (PBMT) group and included 269 MM patients from 6 centers receiving ASCT between Jan 2005 - Dec 2023. We calculated overall survival (OS) from time of ASCT until death by any cause and disease-free survival (DFS) from time of transplant to relapse or death. Results We 269 patients, mean age was 49 years and majority were males (72.9%). Most common presentations were backache (58.4%), anemia (47.6%), renal insufficiency (28.6%) and hypercalcemia (26.8%). Plasmacytomas were present in 23% patients while 52.3% patients had lytic lesions. A monoclonal paraprotein band was detected in 74% patients, IgG kappa in 37% and IgG lambda in 13.9% cases. 13% cases had Light chain myeloma and 6.1% were non-secretory. 33.8% patients had ISS-I, 27.2% had ISS-II and 39 % had ISS-III disease. RISS was available for 33 patients (12.2%). Bortezomib, lenalidomide, dexamethasone (VRd) was used in 41.8% while Bortezomib, Cyclophosphamide, dexamethasone (VCd) in 40.5% patients. Daratumumab based quadruplet was used in 2 patients. Response to induction was not available for 19.5% patients. VGPR or better was documented in 60.7% (SCR in 9.3%, CR in 28%, VGPR in 23.4%). At time of transplant, 21.2% patients were in sCR,37.5% in CR and 20.3% were in VGPR and PR. G-CSF + plerixafor was used in 45.8% patients, G-CSF+ cyclophosphamide in 43.2% and 11 % patients were mobilized with G-CSF alone. Melphalan 200 mg/m 2 was used as conditioning regimen in 51% patients, Melphalan 140 mg/m 2 in 44% patients and 6% received other doses of melphalan. Median CD34 dose was 4.14 × 10 6 /kg. Median neutrophil engraftment was at day 11 and platelet engraftment at day 16. Post transplant consolidation was used in 8.5% cases and 85% patients received post transplant maintenance. For post ASCT maintenance lenalidomide was given in 54.7% and lenalidomide + proteosome inhibitor in 23% patients. OS was 71.4% at a median 72 months while PFS was 55.9% at a median follow up of 47.8 months. For both OS and DFS, detectable paraprotein, ISS stage, response at transplant and conditioning protocol was significant. Both OS and DFS were better in patients undergoing ASCT in CR and better and with Mel200 mg/m 2 . Conclusion Patients receiving ASCT in Pakistan are younger and lack diagnostics for risk stratification. Survival outcomes were better for patients transplanted using Mel200. As bi-specifics and CAR-T cell therapies are not available, all efforts should be made to improve responses to transplant upfront.

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