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    Oral Abstract Session

    OA – 65: Overall Survival (OS) With Ciltacabtagene Autoleucel (Cilta-cel) Versus Standard of Care (SoC) in Lenalidomide (Len)-Refractory Multiple Myeloma (MM): Phase 3 CARTITUDE-4 Study Update

    Friday, September 27, 2024
    5:30 PM – 5:42 PM East Coast USA Time
    Location: Plenary Hall, Pavilion 3
    Introduction: A single cilta-cel infusion significantly improved progression-free survival (PFS; hazard ratio [HR], 0.26 [protocol-specified weighted analysis]; P < 0.0001) vs SoC in patients (pts) with len-refractory MM after 1–3 prior lines of therapy at 16-month (mo) median follow-up in CARTITUDE-4. We report longer-term data, including updated prespecified OS analysis at 34-mo median follow-up.

    Methods: Pts were randomized to cilta-cel or SoC (pomalidomide, bortezomib, and dexamethasone [PVd] or daratumumab, pomalidomide, and dexamethasone [DPd]). Pts assigned to cilta-cel underwent apheresis, bridging therapy (PVd or DPd), lymphodepletion, and cilta-cel infusion (target dose, 0.75 × 106 CAR+ viable T cells/kg). The primary endpoint was PFS. Key secondary endpoints, tested hierarchically, were complete response (CR) or better, overall response, overall minimal residual disease (MRD) negativity (10−5), OS, and time to worsening on the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) total symptom score.

    Results:

    419 pts were randomized (cilta-cel, n=208; SoC, n=211). Median OS was not reached (NR, 95% CI, not estimable [NE]–NE) with cilta-cel or SoC (95% CI, 37.75 mo–NE) (HR, 0.55; 95% CI, 0.39–0.79; P=0.0009); 30-mo OS rates were 76% and 64%, respectively. OS benefit across prespecified subgroups was generally maintained. Median PFS was NR with cilta-cel (95% CI, 34.50 mo–NE) and 11.79 mo (95% CI, 9.66–14.00) with SoC; 30-mo PFS rates were 59% and 26%, respectively. The ≥CR rate was 77% vs 24%, the overall response rate was 85% vs 67%, and the overall MRD-negativity rate was 62% vs 18% with cilta-cel vs SoC, respectively. Median duration of response was NR (95% CI, NE–NE) with cilta-cel and 18.69 mo (95% CI, 12.91-23.72) with SoC. Median time to symptom worsening based on MySIm-Q was NR (95% CI, NE–NE) with cilta-cel and 34.33 mo (95% CI, 32.20–NE) with SoC (HR, 0.38; 95% CI, 0.24–0.61; P < 0.0001). In the safety set (cilta-cel, n=208; SoC, n=208), 97% of pts in each arm had grade (gr) 3/4 treatment-emergent adverse events (TEAEs); cytopenia was the most common. Treatment-emergent infections occurred in 63% and 76% of pts in the cilta-cel and SoC arms, respectively (gr 3/4, 28% vs 30%). Hematologic second primary malignancies occurred in 7 pts (3%) in the cilta-cel arm (myelodysplastic syndrome, n=4 [2 progressed to acute myeloid leukemia {AML}]; AML, n=1; peripheral T-cell lymphoma, n=2) and 1 pt ( < 1%) in the SoC arm (Epstein-Barr virus–associated lymphoma). There were 50 and 82 deaths in the cilta-cel and SoC arms, respectively, of which 21 and 51 were due to progressive disease.

    Conclusions: At ~3 years of follow-up, cilta-cel significantly extended OS, reducing the risk of death vs SoC by 45%, and significantly improved quality-of-life measures vs SoC. Collectively, these data continue to support the overall benefit-risk profile of cilta-cel vs SoC in pts with len-refractory MM as early as after first relapse.