(PA-091) Outcomes of Radiation Therapy Integrated with T-cell Engaging Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma

Introduction: Treatment options are limited for relapsed/refractory multiple myeloma (RRMM) patients (pts) who progress on T-cell engaging bispecific antibodies (bsAb) such as teclistamab (tec) and talquetamab (tal). Radiation therapy (RT) is commonly used for focally progressive or resistant RRMM, but its use with bsAb remains understudied.

Methods: Retrospective single-center study of RRMM pts who received at least one full dose of tec or tal and received RT during their bsAb course. RT was categorized as adjuvant (ART: delivered within the first two bsAb cycles to target pre-existing or early lesions) or rescue (RRT: used for sites of progression after an initial response). BsAb treatment was continued in those receiving rescue radiation.

Results: Our cohort of 41 pts had median age 67.9 years; 34 received tec + RT (22 ART, 16 RRT, 4 both), and 12 received tal + RT (7 ART, 7 RRT, 2 both); 17 received both tec and tal, only 5 received RT during both bsAb courses. Tal pts had more advanced disease (more prior lines (median 5.4 vs 4) and 66.7% prior exposure to anti-BCMA bsAb). Compared to those receiving RRT, pts in the ART group more frequently exhibited adverse disease features at baseline, including elevated ferritin, double-hit cytogenetics, and extramedullary disease (EMD). Median time to RT was 0.1 months (m) in the ART group and 6.9 m in the RRT group. Best overall response rate (encompassing effects of bsAb and RT) was 48.3% (14/29) in the ART and 73.9 (17/23) in the RRT group; ≥VGPR rate was 34.5% (10/29) in the ART group and 47.8% (11/23) in the RRT group. ART + bsAb had median progression-free survival (PFS) of 1.4 m, though 12-m PFS probability was 0.23 (95% CI 0.14-0.54). In the ART group, CRS G1/G2/G3 was seen in 5/3/1 pts and ICANS G1/G2/G3 in 2/3/1 pts. For RRT pts, estimated median PFS after rescue RT was 2.2 m (95% CI 0.92-3.75), and time to next treatment or death (TNTD) was 3.2 m (95% CI 1.5-5.8). In the RRT group, half (15/30) of the courses targeted all known sites of active disease at progression. Pts with rescue RT to all active sites had longer PFS (2.8 vs. 0.9 months, p=0.0015) and TNTD (5.4 vs 1.2 months, p=0.003) after RT compared to pts not treated at all active sites; for these pts, median post-RT PFS was 50% of the pre-RT PFS (range 10% to 250%), and probability of being alive and not requiring subsequent systemic therapy at six months was 0.38 (95% CI 0.16-0.87). RRT pts achieving long-term post-RT PFS ( >12 months) were all on tec. No pts developed CRS or ICANS during RT in RRT group.

Conclusions: RT can be safely used in patients treated with bsAb. ART was associated with short PFS and is likely a marker of aggressive disease, though a subset attained long-term PFS. RRT, particularly when all active disease sites were targeted, yielded additional PFS and time until next therapy or death that is clinically significant in this heavily pre-treated RRMM population.