EMD Associated With Poorer Outcomes in Previously Treated R/R Multiple Myeloma

Efficacy data from the analysis revealed that among patients who were TCE with or without EMD, the median progression-free survival PFS was 4.0 months vs 5.8 months, respectively.

Extramedullary disease (EMD) was associated with poorer outcomes among patients with triple-class–exposed (TCE) relapsed/refractory multiple myeloma, according to results from a retrospective analysis using the Flatiron Health electronic medical records (EMR) presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.1

Efficacy data from the analysis revealed that among patients who were TCE with (n = 175) or without EMD (n = 2259), the median progression-free survival (PFS) was 4.0 months (95% CI, 3.4-4.8) vs 5.8 months (95% CI, 5.3-6.5), respectively. According to the investigators, these data were comparable to prior results from the observational LocoMMotion trial (NCT04035226), which revealed that the median PFS among those with relapsed/refractory multiple myeloma with or without EMD, the median PFS was 2.7 months vs 5.1 months.2

Additionally, the median overall survival (OS) among the EMD vs non-EMD groups was 12.6 months (95% CI, 10.5-17.9) vs 36.4 months (95% CI, 33.4-39.4). Moreover, the time to treatment discontinuation or death (TTD) when excluding patients who underwent CAR-T index regimens was 5.5 months (95% CI, 4.7-6.9) vs 10.0 months (95% CI, 9.2-10.8) in each respective group. Furthermore, the median time to next treatment (TTNT) was 7.0 months (95% CI, 5.7-9.6) vs 12.5 months (95% CI, 11.7-13.3), respectively.

“Among patients with TCE [relapsed/refractory multiple myeloma], the median OS in patients with EMD was only one-third that of patients without EMD… highlighting the need for novel, effective treatment options for patients with TCE [disease] and EMD,” Noa Biran, MD, medical director of Clinical Protocol Data Management and associate professor of medicine of the Multiple Myeloma Division of the John Theurer Cancer Center at Hackensack Meridian Health, wrote in the publication with study coinvestigators.1 “This real-world analysis demonstrated that patients with TCE [relapsed/refractory multiple myeloma], both with and without EMD, are often retreated in a subsequent LOT with the same drugs or drug classes previously administered, underscoring the limited treatment options in this population.”

The real-world, observational study examined patients 18 years or older in the US with relapsed/refractory multiple myeloma who started a subsequent line of treatment after becoming TCE. Patients were identified from the Flatiron Health Research Database with an index date between May 3, 2018, and July 31, 2024.

Those included in the analysis were followed from the index date until the last activity date, death, or end of study period, and were separated into 2 cohorts based on the presence of soft-tissue EMD.

Among the EMD and non-EMD groups, the median age was 66.0 years and 69.0 years, and 50.9% vs 54.6% were male. A total of 65.1% vs 63.3% were White, 72.6% vs 77.2% were non-Hispanic, and 64.0% vs 55.1% had commercial insurance. Moreover, 46.9% vs 58.2% were treated in the community setting compared with 47.4% vs 36.7% in an academic setting, and 41.2% vs 29.4% had high-risk cytogenetics among evaluable patients.

Regarding prior treatment exposure, the median number of prior lines of treatment in the EMD and non-EMD arms was 2.0 and 2.0, respectively. A total of 57.1% vs 52.1% of patients had 1 to 2 prior lines of therapy, and 8.6% vs 8.7% had 5 or more prior lines. Furthermore, 19.4% vs 13.9% were penta-exposed, and 49.7% vs 44.6% underwent prior stem cell transplantation.

In the study, variables included demographic and clinical characteristics, as well as treatment history and patterns. Time-to-event outcomes used included PFS, OS, TTD, and TTNT, and they were estimated using Kaplan-Meier curves. All study variables were reported descriptively.

“[P]atients with TCE [relapsed/refractory multiple myeloma] and EMD consistently experienced poorer outcomes, as evidenced by shorter PFS, OS, TTD, and TTNT compared with patients with TCE [relapsed/refractory multiple myeloma] without EMD,” Biran concluded.1

References

1. Biran N, Harper JS, Min EE, et al. 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. Blood. 2025;146(suppl 1):4582. doi:10.1182/blood-2025-4582
2. Mateos M-V, Weisel K, De Stefano V, et al. LocoMMotion: a study of real-life current standards of care in triple-class exposed patients with relapsed/refractory multiple myeloma – 2-year follow-up (final analysis). Leukemia. 2024;38:2554-2560. doi:10.1038/s41375-024-02404-6