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
Authors: Iftikhar Raheel , Ghani Danyal Ahmad , Chaudhary Ammad Akram , Ali Natasha , Anwar Nida , Bokhari Syed Waqas Imam , Mahnoor Mahnoor , Tariq Hira , Zaidi Uzma , Ahmad Usman , Sarwar Shahzad , Toor Saima Humayun , Iftikhar Ayesha , Ahsan Bushra , Khan Farrukh Ali , Jamal Aisha , Qureshi Fawad , Moosajee Munira , Zahur Umar , Borhany Munira , Mushtaq Muhammad Umair , Adil Salman Naseem , Mir Muhammad Ayaz 
Published: December 2024

Purpose: 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). The purpose of this study was 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 Plasma cell disorders working party of Pakistan Blood and Marrow Transplant (PBMT) group. The study included 269 multiple myeloma patients from 6 centers (both public and private) receiving ASCT between January 2005-December 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 using Kaplan-Meier method and log rank test. Covariates considered were age, type of induction regimen, international prognostic index (IPI) score, depth of response at ASCT, dose of melphalan and use of post-transplant maintenance. A multivariate analysis was done for all variables that were significant (&lt;.05) in univariate analysis.
Results:
Mean age was 49 years (SD=9.49), majority were males (72.9%). Most common presentations were backache (58.4%), anemia (47.6%), renal insufficiency (serum creatinine &gt;177 umol/l in 28.6%) and hypercalcemia (26.8%). IgG kappa was present in 37% patients followed by IgG lambda in 13.9% cases. Thirteen percent cases were of Light chain myeloma while 16.1% were non-secretory. International staging system (ISS) staging was available for 118 patients (43.8%) only. Only 33.8% patients had ISS-I at diagnosis, 27.2% had ISS-II, while 39 % had ISS-III disease. Revised ISS was available for only 33 patients (12.2%) due to non-availability of fluorescent in situ hybridization (FISH) panel. Bortezomib based triplet was most common induction regimen used as first line treatment. Bortezomib, lenalidomide, dexamethasone (VRd) was used in 41.8% while Bortezomib, Cyclophosphamide, dexamethasone (VCd) in 40.5% patients. Very good partial response (VGPR) or better was documented in 60.7% post induction. At time of transplant, 21.2% patients were in sCR,37.5% in CR while 20.3% were each in VGPR and PR. Melphalan 200 mg/m2 was used as conditioning regimen in 51% patients, Melphalan 140 mg/m2 in 44% patients while 6% received other doses of melphalan. Median CD34 dose was 4.14 x 106/kg (IQR 1.3-38.9). Median neutrophil engraftment occurred at day 11 (IQR 9-19) while platelet engraftment at day 16 (IQR 12-45). Post transplant consolidation was used in 8.5% cases while 85% patients received post-transplant maintenance (lenalidomide alone in 54.7% while lenalidomide + proteosome inhibitor in 23% patients).
For the entire cohort overall survival (OS) was 71.4% at a median 72 (95% CI 52.6-92.3) months while progression free survival (PFS) was 55.9% at a median follow-up of 47.8 (95% CI 35.8-59.7) months. Univariate analysis of OS and DFS against following factors was done; age, gender, plasmacytoma, presence of paraprotein, ISS stage, type of induction chemotherapy, response at time of transplant, dose of melphalan, CD34 dose and post transplant maintenance. For both OS and DFS, presence of detectable paraprotein (p=0.034), ISS stage (p=0.02), response at transplant (p=.046) and conditional protocol (p=0.01) was statistically significant. In multivariate analysis, both OS (p=.005, 95% CI .445-.863) and DFS (p=.000, 95% CI 1.03-31.2) were better in patients undergoing ASCT in CR and better and with Mel200 mg/m2 conditioning (for OS p=.041 95% CI 0.276-0.974 while for DFS p=.012, 95% CI 0.083-.024). There was no difference in DFS (p=.99) or OS (p=.229) in patients younger and older than 50 years. Similarly, no difference in OS or DFS was found with respect to gender (p=.942 and p=.891 respectively) and type of induction chemotherapy used, OS (p=.53) and DFS (p=.37).
Conclusion:
Patients receiving ASCT in Pakistan are younger as compared to western data and lack adequate diagnostics for risk stratification incorporating FISH cytogenetics and molecular testing. Survival outcomes were better for patients transplanted in deeper remissions and using Mel200. As bi-specifics and CAR-T cell therapies are not available currently and unlikely to be financially viable in near future, all efforts should be made to improve responses to transplant upfront.