P-028: Characteristics of Bridging Therapy and Impact of Pre-lymphodepletion Tumor Burden on Clinical Outcomes of Idecabtagene Vicleucel

Introduction: Idecabtagene vicleucel (ide-cel) is a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy approved to treat triple-class exposed (TCE) patients with relapsed/refractory multiple myeloma (RRMM) after ≥2 prior lines of therapy. In this initial analysis, we explore the use of bridging therapy (BT) and evaluate the impact of pre-lymphodepletion (pre-LD) tumor burden on ide-cel outcomes in a standard of care (SOC) setting.

Methods: This retrospective study at Moffitt Cancer Center examined TCE RRMM patients with adequate labs to assess response, who received BT before SOC ide-cel between April 15, 2021 and February 20, 2024. Patient characteristics, including BT type and response based on adaptation of IMWG criteria, were analyzed using descriptive statistics. Efficacy and safety outcomes were evaluated, stratified by pre-LD tumor burden (< 50% vs. ≥50% plasma cells).

Results: Of 146 patients who underwent apheresis, 95 (65%) TCE RRMM patients received BT followed by SOC ide-cel, with 23/77 (29.8%) achieving at least a partial response or better among those with measurable disease. The ide-cel overall response rate was higher in BT responders compared to non-responders, although not statistically significant (85% vs. 73%, p=0.4). Several unique BT regimens were used, of which IMiD/CD 38 mAb combinations, alkylators, selinexor, and PI combinations were each observed in >10% of the cohort. Patients with < 6 vs ≥6 prior lines of therapy were more likely to receive an alkylator or IMiD +/- CD 38 mAb combinations (p=0.019). BT responders were less likely to have undergone prior autologous stem cell transplantation (43% vs. 72%, p=0.016). No differences in baseline characteristics by BT regimen time or responses were observed, likely due to limited sample size, heterogeneity in disease characteristics, and BT type. Similarly, safety outcomes did not differ based on BT type or response to bridging.

Patients with low (< 50%, N=35) vs high (≥50%, N=21) pre-LD tumor burden (data available in 56 patients with measurable disease with ≥ 90 days of follow up) showed higher response rates to ide-cel (ORR: 94% vs. 62%, p=0.0046; ≥CR: 60% vs. 29%, p=0.023) and longer progression-free survival (median 13.9 months vs 4.4 months, p=0.0046). Low pre-LD tumor burden was also associated with a significantly lower rate of grade ≥3 CRS compared to high pre-LD tumor burden (0% vs. 13%, p=0.045), while no differences in neurotoxicity were observed.

Conclusions: Heterogeneous BT use for ide-cel-treated patients was observed, without increased safety events. Patients with low pre-LD tumor burden who received BT had lower rates of severe CRS, higher response, and longer PFS. Further research with a larger patient cohort and longer follow-up is warranted to better evaluate the effectiveness of different BT regimens and their impact on ide-cel outcomes.