Treatment of Relapsed/Refractory Myeloma (excluding T-cell redirection therapy)

(OA-55) Treatment Patterns and Outcomes in Quad-Class Exposed (QCE) Relapsed Refractory Multiple Myeloma (RRMM): Investigating Critical Unmet Needs

Saturday, September 20, 2025

11:40 - 11:50 East Coast USA Time

Location: Room 701

Abstract Presenter(s)

Doris K. Hansen, MD

Hematologist/Oncologist
Department of Blood & Marrow Transplant and Cellular Immunotherapy (BMT CI), Moffitt Cancer Center
Tampa, Florida

Introduction: RRMM patients (pts) whose disease relapsed after or is refractory to treatments with proteasome inhibitors (PI), immunomodulatory drugs (IMiD), anti-CD38 antibodies, and anti–B-cell maturation antigen (BCMA) targeting therapies have poor prognoses without an established standard of care. We investigated therapies utilized in real-world practice and associated outcomes for this population, thereby establishing a benchmark for developing novel therapies.

Methods: This retrospective study used data from the Flatiron Health electronic health record database (Jan 1, 2011-Dec 31, 2024) derived from US oncology clinics. Eligible pts were ≥18 years with an MM diagnosis and received ≥3 prior lines of therapy (LOT)—including a PI, IMiD, anti-CD38 antibody, and anti-BCMA therapy—and initiated a subsequent therapy (index date). Pts who received prior anti-GPRC5D therapy or investigational drugs on or after index date were excluded. Patients who had CNS myeloma involvement, plasma cell leukemia, Waldenstrom’s macroglobulinemia, or other invasive malignancy not in remission for ≥2 years before index date were also excluded. Descriptive statistics summarized patient characteristics and treatment patterns. Event (ie, progression, initiation of next treatment, or death)-free survival (EFS) and overall survival (OS) were estimated using the Kaplan–Meier method.

Results: 130 QCE RRMM pts were included: the median age was 68 yrs (range 41-85), 96.9% were RISS stage II-III, 29.2% had high tumor burden (≥50%), and 40.8% exhibited high-risk cytogenetics. Pts had a median of 6 prior lines of therapy (range 3-15): 90% were triple-class (PI, IMiD, CD38) refractory, and 53.8% were quad-class (PI, IMiD, CD38, BCMA) refractory. Index therapies were given between 2020 and 2024 in community (50.8%), academic (43.8%), or both (5.4%) practice settings. The top 5 index therapy classes were infusional chemotherapy (13.8%), anti-BCMA (BsAb, ADC, CAR T; 13.1%), GPRC5D BsAb (11.5%), PI+chemotherapy (6.9%), and PI + anti-CD38 (6.9%). The top 5 index therapy agents were talquetamab (11.5%), teclistamab (8.5%), carfilzomib+isatuximab (4.6%), carfilzomib (3.8%), and cisplatin+cyclophosphamide+etoposide (3.8%). After a median follow-up of 8.8 mo (range 0.2-49.2), 101 (77.7%) pts had an EFS event, and 69 (53.1%) pts died. Median EFS and OS were 4.5 mo (95% CI, 3.5-6.2) and 13.4 mo (95% CI, 10.2-23.2), respectively. For pts receiving anti-BCMA post-QCE, median EFS was 4.9 mo (95% CI, 1.3-10.1), and median OS was 12.9 mo (95% CI, 1.9-NE). For those receiving GPRC5D BsAb post-QCE, median EFS was 4.0 mo (95% CI, 2.3-NE), and median OS was 12.6 mo (95% CI, 4.0-NE).

Conclusions:

QCE RRMM pts were heavily pretreated, with most being triple- or quad-class refractory. Recycling therapies utilizing the same targets resulted in poor EFS and OS. GPRC5D BsAbs offered a new option; however, patients still have poor survival outcomes. Continued therapeutic innovation is critical for this population.