Real-world disease burden and treatment patterns among triple-class–exposed patients with relapsed/refractory multiple myeloma and extramedullary disease in the US: A retrospective analysis using Flatiron Health electronic medical records

Abstract Introduction:Patients (pts) with triple-class exposed (TCE; exposure to ≥1 proteasome inhibitor [PI], ≥1 immunomodulatory drug [IMiD], and ≥1 anti-CD38 monoclonal antibody) relapsed/refractory multiple myeloma (RRMM) have poor outcomes. Prognoses are worse in TCE pts with extramedullary disease (EMD). Real-world (RW) data in this population is scarce. This retrospective study examined the disease burden of pts with TCE RRMM, with and without EMD, who started a subsequent line of therapy (LOT), focusing on pt characteristics, treatment patterns, and clinical outcomes. Methods:Adult TCE pts with RRMM who started a subsequent (index) LOT after becoming TCE, with an index date (index LOT start date) from May 3, 2018 to July 31, 2024, were identified from Flatiron's electronic health record database. EMD and non-EMD pts had presence or absence of soft-tissue EMD (confirmed via chart review) before or on the index date; the non-EMD cohort was used as a descriptive benchmark for the EMD cohort. Pts were followed from index date until the earliest of last activity date, death, or end of study period (January 31, 2025). Study variables, such as demographics, clinical characteristics, treatment history, and treatment patterns, were reported descriptively. Progression-free survival (PFS), overall survival (OS), time to treatment discontinuation or death (TTD), and time to next treatment or death (TTNT) were estimated using the Kaplan-Meier method. Results:A total of 175 EMD pts and 2,259 non-EMD pts were included, with a median follow-up of 10.2 and 16.9 months (mo), respectively. The median ages at index were 66.0 years for EMD pts and 69.0 years for non-EMD pts. Among EMD and non-EMD pts, 49.1% and 45.4% were female, 65.1% and 63.3% were White, 16.6% and 17.4% were Black, and 9.7% and 7.9% were Hispanic/Latino, respectively. The most common insurance types were commercial (64.0% EMD; 55.1% non-EMD) and Medicare, which included both Fee-for-Service and Medicare Advantage plans (38.9% EMD; 43.6% non-EMD). Regarding care setting, 46.9% of EMD pts and 58.2% of non-EMD pts were treated in community practice. Mean (SD) Charlson Comorbidity Index values were 3.5 (3.5) for EMD pts and 2.5 (3.0) for non-EMD pts. Among pts with cytogenetic test data (n=148 EMD; n=1,868 non-EMD), 41.2% of EMD pts and 29.4% of non-EMD pts had a del(17p), t(4;14), or t(14;16) abnormality. Both cohorts had a median of 2.0 prior LOTs before index; among EMD and non-EMD pts, 34.3% and 39.2% had received 3-4 prior LOTs and 8.6% and 8.7% had received ≥5 prior LOTs, respectively. The most common prior treatments among the TCE classes were daratumumab (dara; 100% EMD; 98.2% non-EMD), lenalidomide (96.0% EMD; 97.0% non-EMD), and bortezomib (96.0% EMD; 94.9% non-EMD). Penta-exposure (exposure to ≥2 PIs, ≥2 IMiDs, and ≥1 anti-CD38) was observed in 19.4% of EMD and 13.9% of non-EMD pts; prior stem cell transplant was received by 49.7% and 44.6%, respectively. Among pts with ≥3 mo of follow-up or follow-up ending in death (n=149 EMD; n=2,081 non-EMD), the most common index regimens (excluding corticosteroids) were dara + pomalidomide (pom) (7.4%), carfilzomib (carf) + pom (6.7%), and carf + cyclophosphamide (5.4%) for EMD pts and dara + pom (11.3%), dara + carf (7.4%), and carf + pom (7.2%) for non-EMD pts. The most common drugs within index regimens included carf (39.6%), pom (32.9%), and dara (24.8%) for EMD pts and dara (44.5%), carf (38.4%), and pom (38.0%) for non-EMD pts. Median (95% CI) PFS was 4.0 (3.4-4.8) mo for EMD pts and 5.8 (5.3-6.5) mo for non-EMD pts; median (95% CI) OS was 12.6 (10.5-17.9) mo and 36.4 (33.4-39.4) mo, respectively. Excluding pts with CAR-T index regimens, median (95% CI) TTD was 5.5 (4.7-6.9) mo for EMD pts and 10.0 (9.2-10.8) mo for non-EMD pts. Median (95% CI) TTNT was 7.0 (5.7-9.6) mo for EMD pts and 12.5 (11.7-13.3) mo for non-EMD pts. Conclusions:This RW analysis demonstrates that pts with TCE RRMM, both with and without EMD, are often retreated in a subsequent LOT with the same drugs or drug classes received previously, thus indicating limited treatment options. Moreover, the results underscore the poorer outcomes for pts with TCE RRMM and EMD, as evidenced by shorter PFS, OS, TTD, and TTNT compared to pts with TCE RRMM without EMD. Overall, these findings highlight the critical need for novel, effective treatment options to improve the prognosis of TCE pts with EMD.