Real-world outcomes of patients with multiple myeloma treated with T-cell engagers compared to those treated on clinical trials.

Abstract

e19519 Background: T-cell engagers (TCE) have altered the therapeutic landscape, demonstrating response rates of 60-70% for patients with relapsed/refractory multiple myeloma (RRMM). Median progression free survival (PFS) among the BCMA x CD3 TCEs teclistamab (Tec) and elranatamab (Elran) and the GPRC5D x CD3 TCE talquetamab (Talq) ranges between 10 to 22 months. Yet, many RRMM patients treated in practice would have been ineligible for clinical trials due to stringent inclusion criteria. Methods: A single-center retrospective chart review of consecutive patients with RRMM treated with commercial Tec, Talq, or Elran between 1/1/23-10/31/24 was performed. Baseline patient and disease characteristics, prior treatments, toxicities with TCEs, and clinical outcomes were extracted from electronic records. Descriptive statistics, univariate (UV) and multivariate (MV) analyses were performed. Results: A total of 79 patients who received at least 1 dose of Tec (N=29, 37%), Talq (N=40, 51%), or Elran (N=10, 13%) were evaluated. Most patients (89.8%) would have been ineligible for MajesTEC-1, MomenTAL-1, or MagnetisMM-1 respectively due to BCMA exposure, cytopenias, renal dysfunction, or comorbidities. Twenty-eight (36%) were under-represented minorities (18% Black, 18% Hispanic). High risk cytogenetics were present in 63% of patients and 22% had del(17p). Twenty-nine patients (37%) had extra-medullary disease (EMD). All patients were triple class exposed and 70% were penta-class exposed. About half (44%) were BCMA-exposed. The overall response rate (ORR) was 62%, mPFS was 6.8 months, and median overall survival (OS) was 16.23 months for all patients. Achieving PR or better to the last line of therapy before TCE correlated with improved ORR (p=0.018). Using MV analysis, EMD was associated with inferior OS (HR 2.24; p=0.039). Del(17p) was associated with inferior PFS (HR 2.29; p=0.029). Achieving at least VGPR as best response to TCEs showed a trend toward improved PFS (9.6 mo vs 4.9 mo; p=0.12). The type of TCE product was not associated with PFS or OS. Toxicity was similar to that seen in clinical trials, with 73% of patients experiencing CRS, 10% neurotoxicity, and 46% infections. Conclusions: Our analysis of RW data in RRMM reveals similar safety data but inferior outcomes compared to those treated with TCEs on clinical trials. Factors such as prior BCMA exposure, EMD, an aggressive disease biology wherein patients are unable to enroll on clinical trials due to delays associated with screening and slot allocation may potentially explain the discrepant inferior outcomes in our study. Patients who started therapy following a ≥PR from last line of therapy had improved ORR, implying that TCE benefit may be greater with low burden disease. The absence of differences in the efficacy data amongst the TCEs may suggest that specificity to receptors is not as critical as T-cell fitness.