Fellow University of Connecticut Health Farmington, Connecticut, United States
Introduction: Despite novel therapeutics, multiple myeloma remains incurable with multiple relapses throughout the disease course. In relapsed/refractory multiple myeloma (RRMM), there are several medication classes approved in varying combinations, including anti-CD38 monoclonal antibodies, immunomodulatory drugs (IMiDs), and proteasome inhibitors (PIs), alkylating agents (ALK) amongst others. Despite these advances, there remains a lack of evidence for optimal treatment sequencing in RRMM.
Methods: This is a single center, IRB approved retrospective study of patients with RRMM evaluated at our facility who received at least one treatment regimen for RRMM between the years 2016 and 2023. Data on patient characteristics, treatment regimens and responses were abstracted from the medical record. Responses were recorded by IMWG treatment response criteria as complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD) and Progressive Disease (PD). Suspected complete response (stCR) was also recorded when bone marrow information was not available. Statistical analyses were conducted using R v4.3 software for computing.
Results: 48 patients met inclusion criteria and were included in the analysis, 12 of whom had high risk cytogenetics, with 4 ultra-high risk ( > 1 high risk factor). 20 patients were International Staging System (ISS) stage I, 34 were stage II, and 4 were stage III. Any treatment line that was administered for relapsed disease post induction, autologous SCT consolidation and/or maintenance therapy or primary refractory disease were included. The top four combinations in addition to dexamethasone administered were anti-CD38 drugs combined with IMiD (CD38/IMiD; n=17), anti-CD38 drugs and PIs (CD38/PI; n=16), IMiDs and PIs (IMiD/PI; n=18), and PIs with alkylating agents (PI/ALK; n=19).
Overall response rate (ORR; PR or better) was 64.7% (CD38/IMiD), 56.25% (CD38/PI), 65% (IMiD/PI), and 45% (PI/ALK); (p=0.451,chi -square). CR/stCR rates were: 23.5% (CD38/IMiD), 6.25% (CD38/PI), 25% (IMiD/PI), and 5% (PI/ALK) ;(p=0.144, chi-square). Median Time to next treatment (TNTT) was 43 weeks (CD38/IMiD), 25.5 weeks (CD38/PI), 67 weeks (IMiD/PI), and 45.5 weeks (PI/ALK); p = 0.198, Kruskal-Wallis). When comparing any doublet to triplet regimens, there was no statistical difference in either ORR, 57.69% vs. 52.8%, (p=0.593, chi-square) or CR/stCR rates, 11.53% vs. 13.48%, respectively (p=0.122,chi-square).
Conclusions: Whilst no significant differences were observed between specific treatment combinations in our RRMM population, there were notable trends toward improved response rates and TNTT in CD38/IMiD and IMiD/PI groups when compared to CD38/PI group. Further, no statistically significant response rate in doublet vs. triplet regimens was observed, raising the question of selecting truly synergistic drug combinations as well as optimal number of drugs in a treatment regimen for improved efficacy and decreased treatment related toxicity.
