A Single Center Real-World Data Comparing Salvage Autologous Hematopoietic Stem-Cell Transplantation, Selinexor Combo and Elranatamab Alone Among Triple Class Refractory Myeloma Patients: Better Efficacy with Elranatamab

Introduction: A vast majority of multiple myeloma (MM) patients may experience relapse and require multiple lines of therapy. The choice of the next treatment depends on multiple factors including the response, tolerance to prior therapies, as well as access to novel treatments. Among triple-class refractory patients, in real-world settings where CAR-T therapies are not available, options are limited. Here we report a single-center experience comparing salvage autologous hematopoietic stem-cell transplantation (sAHCT), selinexor combinations, and elranatamab in this highly unmet needed group.

Patients & Methods: Between January 2015 and June 2023, 50 patients at our center underwent sAHCT for treatment of refractoriness to all available drugs. Salvage AHCT is defined as being transplanted for treatment of MM after evidence of disease progression not responding to second-generation proteasome inhibitors (PI), immunomodulating agents (IMID), or antiCD38 monoclonal antibody. We compared the outcomes of these patients with RRMM patients who had exhausted their treatment options and were progressing on their last line of therapy to receive single agent Elranatamab at a step-up dosing starting with escalating to 72 mg once a week for six months and on alternate weeks thereafter. Selinexor was administered with either Bortezomib(n:8) or Pomalidomide(n:9) at a dose of 60-100 mg/week every 5-6 weeks. Response and disease progression were assessed according to the IMWG criteria.

Results: Patients' characteristics and the outcomes are shown in Table. The median age of patients was similar in both groups. Patients were heavily treated with a median of 4 prior lines of therapy (1-17) and 7 out of 13 carried high-risk cytogenetics in elranatamab group. All patients were triple-class refractory. Five patients responded to DCEP bridging therapy prior to sAHCT. Selinexor (n: 11, 64.7%) and elranatamab (n:5 patients,38.5%) were administered after sAHCT. One patient underwent sAHCT due to progression under Selinexor treatment. In the sAHCT group, 68% of patients relapsed within a median of 7.4 months. Median DFS was significantly prolonged with single agent elranatamab (NR) compared to sAHCT (7.3 mos) and Selinexor-combos (7.3 mos) (p=0.4) (Figure). Adverse events on selinexor regimens included fatigue, nausea, and thrombocytopenia which were managed with Selinexor dose adjustment and supportive care. All patients received the recommended step-up priming dose elranatamab regimen, 69.2% of our patients experienced a Grade 1 cytokine release syndrome (CRS) during the first cycle. None of these patients had to stop treatment due to toxicity. Early sAHSCT mortality was not observed either. At the time of the analysis, all patients on Selinexor have progressed after a median follow-up of 14.7 months. Elranatamab patients are currently at 5 months follow-up and 7/ 13 are still on treatment.

Conclusion: Upfront AHCT is a cost-effective treatment option with a decreasing efficacy in late relapses. In this RWE study, we have been able to confirm the inferiority of AHCT at late stages. As seen in our series cytogenetic profile worsens with an increase in the prior number of lines of treatment which are both highest among patients who have received elranatamab. Despite these unfavorable features, single-agent elranatamab has been able to attain the highest overall response rates, unfortunately not reflecting on PFS yet, due to short follow-up. Furthermore, two of these had progressed while on a BCMA immunotoxin Rx and have responded to elranatamab. In conclusion, even with short follow-up single-agent elranatamab is a tolerable and highly effective regimen