Second Autologous Transplantation in Multiple Myeloma with Renal Dysfunction

Introduction Autologous stem cell transplant (ASCT) as a salvage option in patients (pts) with late relapse (≥18 months after upfront ASCT) represents an effective therapy and can prolong response in Multiple Myeloma (MM). Presence of comorbidities such as renal dysfunction can limit treatment options and impact ASCT eligibility. Efficacy and safety data supporting a second ASCT in pts with renal dysfunction for relapsed disease are limited. Methods All adult pts with MM with renal dysfunction undergoing a non-tandem second ASCT at our institution between January 2006 and January 2019 were identified. Renal dysfunction was defined as pre-transplant creatinine clearance ≤ 60 ml/min. Demographics, disease characteristics, and treatment history were compiled. Relapse free survival (RFS), overall survival (OS), relapse rate, and non-relapse mortality (NRM) outcomes were assessed. RFS durations after both the first and second ASCTs for each pt were compared using a paired log-rank test and corresponding hazard ratios (HR) was estimated using a paired cox proportional hazards regression model through mixed-effects models. Results Thirty six pts with renal dysfunction underwent a second ASCT at our institution. Fourteen pts (39%) had progressive disease (PD) and 9 pts (25%) had very good partial response or better. Median time between first and second ASCT was 57.05 months (18.98-103.25). Conditioning regimens included: ≤140 mg/m2 Melphalan (MEL) (61%; n=22), >140 mg/m2 MEL (28%; n=10) and BEAM (8.3%; n=3). Median length of hospitalization during second ASCT was 18 days (Range, 11-74). Median time to granulocyte and platelet engraftment was 12 (9-16) and 19 (0-61) days, respectively. In hospital events included: treatment-requiring infections in 15 pts (41.7%) and cardiac complications in 5 pts (13.9%). Four pts (11.1%) required intensive/critical care admission. By day 100 (d100) assessment, 30 of 34 surviving pts (83% by ITT) had stable disease or better, and 4 pts (11%) had PD. Twenty pts (58.8%) had an improvement in disease status compared to their pre-ASCT status, while 8 pts (23.5%) maintained their pre-ASCT disease status. Five pts (14%) were readmitted by d100, with 2 pts requiring intensive care. One of 2 pts on dialysis pre-second ASCT became dialysis independent. From second ASCT, median RFS was 1.04 yrs (95% CI, 0.74 to 1.67) and median OS was 3.34 yrs (95% CI, 3.30 to 7.99; median follow up 4.31 yrs); respectively. The cumulative incidence rates for relapse and NRM at 1 yr after second ASCT were 37.1% and 5.6%, respectively. By MVA, light chain MM was associated with higher relapse rate (p=0.03) and lower NRM (p=0.01). Conclusion Our data suggests that second ASCT is well tolerated with low complication /readmission rates in patients with renal dysfunction. Second ASCT as salvage can provide disease control for more than a year for these patients who may have limited treatment options.