MM-522 Effectiveness of Bridging Therapy Corresponds to Improved Outcomes After Receiving CAR-T Therapy: Phase 3 CARTITUDE-4 Study of Patients With Relapsed, Lenalidomide-Refractory Multiple Myeloma

In the phase 3 CARTITUDE-4 trial, patients who received ciltacabtagene autoleucel (cilta-cel) as study treatment (ie, did not have disease progression before cilta-cel infusion), had high rates of overall response (99.4%), complete response or better (86.4%), and 12-month progression-free survival (PFS; 89.7% from randomization). Bridging therapy controls disease while CAR-T cell therapy is being manufactured and potentially reduces the risk of toxicities by debulking. The impact of disease control prior to CAR-T infusion on postinfusion clinical outcomes is not well established. We present post hoc analyses describing cilta-cel efficacy by response to bridging therapy in patients who received cilta-cel as study treatment in CARTITUDE-4. Patients in the cilta-cel arm underwent apheresis, received bridging therapy with either pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd), and then a single cilta-cel infusion 5–7 days after the start of lymphodepletion. PFS (measured from randomization) was analyzed in patients who had a ≥25% reduction in paraprotein from baseline to the start of lymphodepletion vs others (paraprotein either increased, no change, or <25% reduction). In vivo effector-to-target (E:T) ratio was derived by peak CAR-T cell expansion normalized to pre-infusion serum soluble BCMA levels. Among 176 patients who received cilta-cel as study treatment (DPd, n=158; PVd, n=18), 148 had a ≥25% reduction in paraprotein during the bridging period. At 15.9-month median follow-up, median PFS was not reached (95% CI, not estimable [NE]-NE) in patients with ≥25% reduction vs 19.2 months (95% CI, 15.8-NE) in the others (HR, 0.32; 95% CI, 0.16-0.66). Estimated 12-month PFS rates were 91.8% and 78.1%, respectively. In patients with available biomarker data (n=171), a significantly higher in vivo E:T ratio was observed in those with a ≥25% reduction in paraprotein vs the others (median [IQR], 62.6 [139.2] vs 5.4 [62.3]). Greater response to bridging therapy (≥25% paraprotein reduction) correlated with longer PFS. This may be explained mechanistically by a higher in vivo E:T ratio, previously shown to be associated with longer PFS (Montes de la Oca, ASH 2023). These data emphasize the importance of optimized bridging therapy for disease control prior to receiving cilta-cel.