Cellular and T cell engager Immunotherapy

Ciltacabtagene Autoleucel vs Standard of Care in Patients With Functionally High-Risk Multiple Myeloma: CARTITUDE-4 Subgroup Analysis

P-082: Ciltacabtagene Autoleucel vs Standard of Care in Patients With Functionally High-Risk Multiple Myeloma: CARTITUDE-4 Subgroup Analysis

Friday, September 27, 2024

Surbhi Sidana, surbhi.sidana@stanford.edu

Assistant Professor
Stanford University, United States

Introduction: Functionally high-risk (FHR) multiple myeloma (MM) is associated with poor prognosis. In CARTITUDE-4, a single ciltacabtagene autoleucel (cilta-cel) infusion significantly improved progression-free survival (PFS) vs established standard of care (SOC; P< .0001) in patients (pts) with lenalidomide (len)-refractory MM after 1–3 prior lines of treatment (tx; LOT). This post hoc subgroup analysis of CARTITUDE-4 reports outcomes for pts who received cilta-cel vs SOC as second-line (2L) tx, including pts with FHR MM.

Methods: Pts randomized to cilta-cel underwent apheresis, received PVd or DPd bridging tx, and then cilta-cel infusion (target dose, 0.75×10⁶ CAR+ viable T cells/kg) 5–7 d after the start of lymphodepletion. Pts randomized to SOC received PVd or DPd until progressive disease (PD). FHR was defined as PD within 18 mo after receiving autologous SCT or the start of initial frontline tx. Efficacy was assessed in randomized pts (intent to treat) and safety in pts who received any part of study tx.

Results: 136 pts received cilta-cel (n=68) or SOC (n=68) as 2L tx. Of these, 79 had FHR MM (cilta-cel, n=40; SOC, n=39). Median PFS was longer in pts who received cilta-cel (not reached [NR]; 95% CI not evaluable [NE]–NE) vs SOC (17 mo; 95% CI 11–NE; hazard ratio [HR] 0.35; 95% CI 0.2–0.7; P=.0007) as 2L tx including the FHR subset (NR; 95% CI 18–NE, vs 12 mo; 95% CI 8–NE; HR 0.27; 95% CI 0.1–0.6; P=.0006). The 12-mo PFS rate was also longer for pts receiving cilta-cel vs SOC as 2L tx (78%; 95% CI 66–86 vs 59%; 95% CI 46–69) and included the FHR subset (77%; 95% CI 60–87 vs 49%; 95% CI 32–64). Overall survival was immature at the time of this analysis. The overall response rate of pts who received 2L cilta-cel (90%) was greater than SOC (79%; odds ratio [OR] 2.3; 95% CI 0.8–6.0; P=.0979), similar to FHR pts (88% vs 80%; OR 1.8; 95% CI 0.5–6.1; P=.3400). Complete response or better was achieved in 71% of pts receiving cilta-cel vs 35% with SOC (OR 4.4; 95% CI 2.1–9.0; P< .0001) as 2L tx and 68% vs 39% in those with FHR (OR 3.3; 95% CI 1.3–8.4; P=.0102). More pts achieved minimal residual disease negativity at a 10^–5 threshold with cilta-cel (63%) vs SOC (19%; OR 7.3; 95% CI 3.3–15.9; P< .0001) as 2L tx and with FHR pts (65% vs 10%; OR 16.3; 95% CI 4.8–55.1; P< .0001). A longer median duration of response was achieved in all pts receiving cilta-cel (NR; 95% CI NE–NE) vs SOC (20 mo; 95% CI 14–NE) and in FHR pts (NR; 95% CI 16–NE vs 16 mo; 95% CI 8–NE). Pts with grade ≥3 TEAEs who received cilta-cel vs SOC as 2L tx were comparable (96% vs 96%) including the subset with FHR MM (100% vs 97%). Among pts who received 2L tx, 22 died (cilta-cel, n=11; SOC, n=11), 16 of whom had FHR MM (n=7; n=9).

Conclusions: In pts with len-refractory FHR MM after 1 prior LOT, cilta-cel improved outcomes vs SOC and had a safety profile consistent with the known mechanism of action of CAR-T tx, suggesting cilta-cel may overcome the poor prognosis associated with FHR MM.