Effect of dose-adjusted melphalan on MRD-negativity to full dose melphalan in patients with multiple myeloma post-autologous stem cell transplant.

person Jeries Kort University Hospitals Cleveland Medical Center/ Case Comprehensive Cancer Center, Cleveland, OH info_outline Jeries Kort, James John Ignatz-Hoover, Nikolas Naleid, Frank Oley, Brenda W. Cooper

Authors person Jeries Kort University Hospitals Cleveland Medical Center/ Case Comprehensive Cancer Center, Cleveland, OH info_outline Jeries Kort, James John Ignatz-Hoover, Nikolas Naleid, Frank Oley, Brenda W. Cooper Organizations University Hospitals Cleveland Medical Center/ Case Comprehensive Cancer Center, Cleveland, OH, Univ Hosps of Cleveland/Case Western Reserve Univ, Cleveland, OH, Department of Internal Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, University Hospitals Cleveland Medical Center, Cleveland, OH Abstract Disclosures Research Funding No funding sources reported Background: Despite significant therapeutic advancements, Multiple Myeloma (MM) remains an incurable disease. Autologous stem cell transplantation (ASCT) is a standard treatment for eligible patients, with high-dose melphalan (MEL200) as the preferred conditioning regimen. Reduced-dose melphalan (MEL140) is used for older or less fit patients. However, this was not prospectively studied and there has been ongoing debate about the efficacy of reduced dosing. This study aimed to investigate the impact of melphalan dose on minimal residual disease (MRD) negativity rates in MM patients undergoing upfront ASCT. Methods: We conducted a retrospective, single-center study involving 74 MM patients who underwent ASCT between 2018 and 2022 at UHCMC, Cleveland, OH and had MRD testing done after transplant. MRD testing was performed using the ClonoSEQ next generation sequencing platform. Results: Median age was higher in the MEL140 group compared to MEL200 (70.3 vs 59.8 years), both groups were similar in terms of sex and race distribution, BMI and KPS scores. Both groups have comparable ISS staging and high-risk cytogenetics. Similar numbers of lines of treatment prior to transplant were seen, with approximately 64% having only one line. First-line induction therapy included triplet therapy (Lenalidomide, Bortezomib, and Dexamethasone) in 73% of patients. Depth of remission at transplant was comparable between groups. MRD negativity rates at 10 -5 and 10 -6 were comparable between MEL140 and MEL200 groups (64% and 39% in MEL140; 61% and 41% in MEL200; p=0.8 and 0.7 respectively). Sustained MRD negativity at 10 -5 over at least 12 months was also comparable (43% in MEL140; 50% in MEL200, p=0.8). After a median follow-up of 37 months, PFS was not reached for either group (p=0.69). Patients achieving MRD negativity at levels of 10 -5 had a not reached median PFS, while those not achieving MRD negativity had a median PFS of 41 months (95%CI 23-NR; p=0.024). There was no significant difference in hospital stay duration, time to neutrophil engraftment, readmission rate, or infections within 100 days post-transplant between the MEL140 and MEL200 groups. Conclusions: Our real-world analysis demonstrates that MEL140 yields similar deep post-transplant remissions as MEL200, translating to improved PFS for patients achieving MRD negativity, regardless of the dose used. This is the first report to our knowledge of MRD negativity rate in patients receiving MEL140. MEL 140 N = 28 MEL200 N = 46 P-value Hospital Stay (d) 15.07 (2.14) 15.61 (5.51) 0.3 Readmissions 4(14%) 10(22%) 0.4 Infections 4(14%) 9(20%) 0.8 MRD negativity 10 -5 18(64%) 28(61%) 0.8 MRD negativity 10 -6 11(39%) 20(43%) 0.7 Sustained MRD negativity 10 -5 12(43%) 23(50%) 0.8