Pb2113: treatment refractoriness and response rates in patients with relapsed/refractory multiple myeloma: a retrospective analysis of real-world data

Background: Despite significant progress in the treatment of multiple myeloma (MM), relapse rates remain high, leading to shorter response periods, poor prognosis, and lower survival rates, even with subsequent treatments. Aims: Given the limited real-world evidence, this study aimed to assess the treatment refractoriness and response rates among patients with relapsed and/or refractory MM. Methods: This was a retrospective study conducted among relapsed and/or refractory MM patients using a commercial registry. Patients were included in the study if they a) were 18-79 years of age at the time of diagnosis; b) received ≥ 5 lines of therapy; c) were exposed to at least one proteasome inhibitor (PI), one immunomodulatory drug (IMiD), and one CD38-targeting monoclonal antibody (CD38 MoAB); and d) had the last MM related visit before October 2022. Patients were excluded if they had concurrent primary malignancies or recorded death within 28 days of the last line initiation. Patients’ response status was defined by the International Myeloma Working Group (IMWG) Response Criteria (2016). Patients were categorized as “responders” if their response status lasted for at least 28 days. Refractoriness was defined by IMWG Response Criteria as progression while on treatment or within 60 days of treatment discontinuation. The class of refractoriness was additionally determined for each patient. “Penta-class” was defined as refractoriness to 1 CD38 MoAB + 2 PIs + 2 IMiDs, “triple-class” as refractoriness to an IMiD, a PI, and a CD38 MoAB, and “dual-class” as refractoriness to an IMiD and a PI. “Not triple” refractory was defined as refractoriness to 1 CD38 MoAB, and not both of a PI and an IMiD. Results: A total of 283 patients were included in the study with an age range of 27-78 years (median: 65). Patients received a median of 6 lines of therapy ranging from 5 to 21. The overall response rate among the patients was 35.7% (101 out of 283), with a median response duration of 6.3 months (range: 0.9-53.4). The majority of patients were classified as penta-refractory (33.6%), followed by dual-refractory (32.9%), triple-refractory (25.4%), and not triple-refractory classes (13.4%). The response rates were 49.1% in patients with dual-class, 44.7% in not triple-refractory, 33.7% in penta-class, and 22.2% in triple-class refractory. Summary/Conclusion: This real-world study indicates that a significant portion of patients continue to experience treatment refractoriness and have a low response rate even after multiple lines of therapy. These findings highlight the need for continued efforts to improve treatment outcomes and address the challenges of MM relapse and refractoriness. Keywords: relapsed/refractory, Multiple myeloma, Real world data