3705 - Clinical Outcomes Following Bridging Radiotherapy in Relapsed/Refractory Multiple Myeloma Patients prior to Chimeric Antigen Receptor T-Cell Therapy

Purpose/Objective(s): The role of bridging RT (BRT) prior to anti-BCMA chimeric antigen receptor T-cell (CAR T) therapy in relapsed/refractory multiple myeloma (RRMM) patients remains undefined. We report our single-institution experience of administering BRT prior to anti-BCMA CAR T and evaluate its effectiveness in treating sites of extramedullary disease (EMD).

Materials/Methods: We identified all RRMM patients who received BRT within 90 days of CAR T infusion from 2020 to 2025. Patient and disease characteristics were recorded using a prospectively maintained database. Clinical outcomes and radiation regimens were retrospectively reviewed. EMD was defined as both paraskeletal plasmacytomas and visceral/soft tissue plasmacytomas not contiguous with bone marrow. Comprehensive BRT was defined as radiation to all sites of EMD. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method from CAR T infusion and compared using log-rank analysis. Local failure was defined as recurrent disease within a previously irradiated site. BRT toxicities were graded using CTCAE v5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to ASTCT criteria.

Results: We identified 15 patients who underwent BRT to 22 lesions prior to CAR T. Most were male with a median age of 60 and underwent a median of 5 prior lines of therapy. Ten patients received cilta-cel, while 5 received ide-cel. At a median follow-up of 7.0 months, 8 patients experienced disease progression yielding a median PFS of 6.7 months. Median OS was not reached. Among those who progressed, 63% showed no evidence of bone marrow involvement, with all 8 developing distant plasmacytomas. Seven patients underwent BRT to sites of EMD, while 8 patients received BRT for painful bone metastases. Patients with pretreatment EMD trended to inferior PFS (6.9 v. 10.1 mo., p = .06). However, with the subset of EMD patients, those receiving comprehensive BRT (n = 4) demonstrated superior PFS (6.8 v. 4.7 mo., p = .05). 22 lesions were irradiated prior to CAR T, including 10 sites of EMD and 12 isolated bone lesions. The median interval from BRT to CAR T infusion was 34 days. The most common dose/fractionation schedules were 20Gy in 5 fractions (n = 6, 27%) and 8Gy in 1 fraction (n = 6, 27%). None of the irradiated lesions developed a local recurrence. No grade =3 BRT toxicities were observed. Two patients (13%) experienced grade 2 CRS; one patient (7.5%) developed grade 2 ICANS. No grade =3 CRS or ICANS occurred.

Conclusion: BRT prior to anti-BCMA CAR-T therapy appears to be a safe and tolerable treatment strategy, with no grade =3 toxicities. None of the irradiated lesions developed local failure following BRT, albeit within a limited follow-up period. EMD continues to be associated with inferior clinical outcomes. Comprehensive BRT to all sites of EMD prior to CAR T may be associated with improved PFS, but further evaluation with longer follow-up and larger cohorts is warranted.