DP110 | INFECTIONS AND IMMUNE RECONSTITUTION IN THE PHASE 3 CARTITUDE-4 TRIAL OF CILTACABTAGENE AUTOLEUCEL VS STANDARD CARE IN LENALIDOMIDE-REFRACTORY MULTIPLE MYELOMA AND 1–3 PRIOR LINES

Patients (pts) with multiple myeloma (MM) have high risk of infection. We characterize infections and immune reconstitution in pts receiving ciltacabtagene autoleucel (cilta-cel) vs standard care (SOC) treatment (tx) in CARTITUDE-4 (NCT04181827). Eligibility criteria were previously described. Cilta-cel arm pts underwent apheresis, received bridging tx (daratumumab-pomalidomide-dexamethasone [DPd]/pomalidomide-bortezomib-dexamethasone [PVd]), and cilta-cel infusion 5–7 days [d] post lymphodepletion. SOC arm pts received DPd/PVd until progressive disease (PD). Infection was assessed in all pts receiving any part of study tx (safety set) and pts receiving cilta-cel as study tx. Lymphocyte counts were derived by flow cytometry. As of Apr 2023 (21.5 months [mo] median follow-up), 91% of the cilta-cel arm (n=208) and 72% of the SOC arm (n=208) had either tx-emergent hypogammaglobulinemia or postbaseline IgG <500 mg/dL; 68% and 16% received intravenous immunoglobulin (IVIG), respectively. 30% and 23%, respectively, had grade (gr) 3/4 infections. In mo 1–3, mo 4–6, mo 7–9, and mo 10–12 post study tx start, a respective 26, 18, 12, and 9 pts in the cilta-cel arm and 18, 9, 14, and 6 in the SOC arm had gr 3/4 infections. 11 (5%) pts in the cilta-cel arm and 6 (3%) in the SOC arm had fatal infections, mostly due to COVID-19 pneumonia (7 and 2 pts, respectively). Any gr viral infections occurred in 42% and 37% of pts, respectively, any gr bacterial infections in 17% and 18%, and any gr fungal infections in 6% and 7%. Among 176 pts receiving cilta-cel as study tx, 24% had gr 3/4 infections; most occurred in the first 3 mo post-infusion (23 in mo 1–3; 11 in mo 4–6; 8 in mo 7–9; 4 in mo 10–12; Figure 1). 11 had a fatal infection, including 7 COVID-19–related deaths. 8/11 deaths from infections occurred in the first 6 mo. 85% of pts had gr 3/4 neutropenia that recovered to gr ≤2 by d 60. B cells recovered by ~6–7 mo in bone marrow (BM) and ~9 mo in blood; plasma cells recovered by ~9 mo in BM and blood. IgA and IgM recovery was seen in the cilta-cel arm only. Pts in both arms were at risk of severe and fatal infections. In the cilta-cel arm, most severe and fatal infections occurred early after infusion, with risk higher in the first 3–6 mo and decreasing over time. These results underscore the importance of monitoring, infection prophylaxis (eg, IVIG), and supportive care early following cilta-cel infusion and throughout for pts receiving continuous tx.