Factors Limiting Availability of Autologous Stem Cell Transplantation in Multiple Myeloma Patients: Insights from a Multicenter Collaborative Study of Society of Medical Oncology, Pakistan Blood and Marrow Transplant Group, Pakistan Society of Clinical Oncology
Authors: Chaudhary Ammad Akram , Iftikhar Raheel , Ahmed Usman , Mahmood Humera , Gilani Mehwish , Masood Misbah , Anwar Nida , Aalam Abro Nargis , Ahmed Khan Zeeshan , Moosajee Munira , Aziz Zeba 
Published: December 2024

PurposeUtilization of autologous stem cell transplant (ASCT) for newly diagnosed multiple myeloma (MM) patients in Low and Middle Income Countries (LMIC) is limited due to multiple factors. The purpose of this study was to report the factors limiting ASCT in MM patients in LMICs.
Methods This multicenter, retrospective observational study was done as a collaborative project. We reviewed data of 421 transplant ineligible MM cases from 8 different centers across Pakistan from November 2007 to November 2022. Only 115 MM patients with a documented reason for transplant ineligibility were selected. We collected the data for various factors leading to transplant ineligibility, for example, advanced age, co-morbidities, lack of finances, frailty, poor prognosis, loss to follow-up and death. Data was entered and analyzed on SPSS (Statistical Package for the Social Sciences). Frequency and percentages were calculated. Mean and Standard Deviation were computed for descriptive variables while categorical variables were analyzed by Chi-Square test.
Results: Our study included 115 patients, median age at diagnosis was 60 years (IQR 52 -70), with 71 (61.7%) being males and 44 (38.3%) females. Most common presentations were backache in 59 cases (51.3%), anemia in 59 (51.3%) cases and renal insufficiency in 36 (31.3%). Only 9 (7.8%) had hypercalcemia and 11 (9.5%) cases had plasmacytoma. Total of 80 (69.6%) cases had evidence of lytic lesions on skeletal survey. Serum Protein Electrophoresis (SPEP) was positive in 46 (40%), Negative in 8 (7 %) and data was missing in 61 (53 %) cases. Serum Immunofixation (IF) was positive for 73 (63.5%) cases, negative in 5 (4.3 %) cases and missing for 37 (32.2%) cases. Only 5 (4.3%) cases had positive urine immunofixation, while it was negative in 23 (20%) cases and data was missing for 87 (75.5%) cases. International staging system (ISS) staging was available for (49.6%) patients. Out of these, 3 (2.6 %) patients were ISS-1, 21 (18.3 %) were ISS-2, 33(28.7 %) cases were ISS-3 and data was missing for 58 (50.4 %) patients. Around 12 (10.4%) cases were treated with Bortezomib and Dexamethasone (BorDex), 51 (44.3%) with Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD), 19 (16.5%) with Lenalidomide and Dexamethasone (LenDex), 8 (7%) with Thalidomide and Dexamethasone (Thal-Dex), 4 (3.5%) with Bortezomib, Lenalidomide and Dexmethasone (VLD) and 4 (3.5%) cases with Melphalan and Prednisolone (Mel-Pred). Treatment data was missing for 16 cases. Best response cat was mentioned for 32 (27.8 %) cases, with 14 (12.2%) having CR, 4 (3.5%) having sCR, 10 (8.7%) having VGPR and 4 (3.5%) having PR. Response details were missing for 83 (72.2%) cases. The commonest factor for ASCT ineligibility were advance age and lack of finances. Out of the cohort, 32 (27.8 %) cases were transplant ineligible on advance age. Their median age was 73 years (IQR 60-80). On the other hand, 21 (18.3 %) lacked finances for ASCT, having median age of 59 years (IQR 37-68). Fifteen (13 %) cases were declared unfit for ASCT on poor prognosis, however details of reason for deferral, functional or remission status were not mentioned. Median age of this group was 57 years (IQR 42-67). Nine (7.8 %) were declared ASCT ineligible on co-morbidities having median age 51 years (IQR 45-73 years). Only 4 cases had renal impairment and 3 cases were dialysis dependent. EF was less than 60% in 5 (55.5%) patients. One patient also had evidence of cardiac amyloidosis, but the modality of evaluation of cardiac amyloid was not mentioned. Fifteen (13 %) cases were declared ineligible on frailty. Amongst them, 2 cases were also unfit on advanced age. This was depite the presence of low mean frailty score (1.92 + 0.95). Last follow-up data was available for 96 (83.4 %). The median days of follow-up for these cases was 380 days. From this cohort, 68 (59.1%) cases were lost to follow-up, 28 (24.3 %) were reported alive and 11 (9.6%) cases were reported dead.
Conclusion:
Despite evidence suggesting survival benefit of early transplant in MM, there is extremely low referral rate for ASCT in Pakistan. Most common reasons for declaring transplant ineligibility were age, renal dysfunction, fraility despite patients being younger and having low fraility score. Lack of finances was another commonly cited reason. There is a need for physicians' awareness regarding early transplant referrals and liaison with governmental agencies for arranging finances for transplant.