Treatment Patterns and Outcomes in Triple-Class Exposed Patients with Relapsed and Refractory Multiple Myeloma: Findings from the Flatiron Database
Authors: Sidana Surbhi , Thirumalai Dhanalakshmi , Itani Taha , Baro Elande , Giordana Monique , Granados Enrique , Hasegawa Ken , Rosado Margrit B , Chan Rebecca J , Kostic Ana , Banerjee Kamalika , Patel Krina K. , Hansen Doris K. 
Published: December 2024

Introduction: The rapidly evolving treatment landscape for patients (pts) with triple-class exposed relapsed/refractory multiple myeloma (RRMM)-those exposed to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies-in the fourth line or higher (4L+) setting warrants closer examination. This analysis aims to describe patient characteristics, treatment patterns, and clinical outcomes (overall response rate [ORR], duration of response [DOR], time to next treatment [TTNT], progression-free survival [PFS], and overall survival [OS]) in pts with triple-class exposed 4L+ RRMM in real-world clinical practice in the United States (US).
Methods: This retrospective cohort study utilized the Flatiron Health electronic health record (EHR)-derived and de-identified database, focusing on adult pts with RRMM who were triple-class exposed, had been treated with at least three prior lines of systemic therapy, and were refractory to their last line of therapy (LOT). Pts with a history of plasma cell leukemia were excluded. The study period was from November 16, 2015, to December 31, 2023. After meeting the eligibility criteria, the start date of the first subsequent LOT was defined as the index date. LOT was determined based on evidence of disease progression and assessed based on the IMWG criteria using serum or urine M-protein values or free light chains (FLC) values. Response to therapy was assessed using a derived response algorithm based on Flexible IMWG criteria (Xu et al., 2023). Descriptive statistics were used to summarize patient and disease characteristics as well as treatment patterns. ORR was defined as the number and percentage of pts with at least a derived partial response or better to the index LOT. Time-to-event outcomes were estimated using the Kaplan-Meier method and presented with their respective two-sided 95% confidence intervals (CIs).
Results: A total of 594 pts were included in this analysis. The median age at index was 72 years (range, 36-85 years), and 53.0% of patients were male. Pts had a diverse racial background: 64.6% White, 17.2% African American, 11.4% other and 6.7% missing/unknown. Most patients (66.8%) were treated in the community setting. At diagnosis, 61.6% presented with IgG multiple myeloma. For those with available test data at index LOT (n=452), half (50.4%) had high-risk cytogenetics. The median number of prior lines of therapy was 3 (range, 3-12); 61.3% and 9.6% of patients had triple-refractory and penta-refractory disease prior to index date, respectively. There were 224 unique treatment combinations, with regimens comprised of daratumumab, dexamethasone, and pomalidomide (n=57, 9.5%) being the most common index LOT. About 70% of the treatments received at index were anti-CD38- based regimens, with B-cell maturation antigen (BCMA)-targeted therapies constituting 15.7% of treatments administered on or after the index date. The median follow-up time from index was 9.6 months. The ORR was 34.0% (95% CI: 29.7-37.5) with a median DOR of 4.9 months (95% CI: 4.1-6.0). The median TTNT, PFS and OS were 6.3 months (95% CI: 5.4-6.9), 4.1 months (95% CI: 3.6-4.6), and 15.4 months (95% CI: 13.7-18.6), respectively. OS tended to be longer in females (median OS=20.1 months; 95% CI: 15.4-25.2) than males (median OS=13.8; 95% CI: 11.5-16.0), and in African Americans (median OS=23.0 months; 95% CI: 11.5-27.4) than Whites (median OS=15.1; 95% CI: 12.9-18.4).
Conclusion: This study underscores the heterogeneity and lack of a standard of care in treating triple-class exposed RRMM patients in the 4L+ setting. Despite the introduction of newer treatment modalities, clinical outcomes for these patients remain suboptimal, emphasizing the urgent need for more effective and durable therapies.