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Ciltacabtagene Autoleucel, a BCell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy, in Lenalidomide-Refractory Patients With Progressive Multiple Myeloma After 1-3 Prior Lines of Therapy: Updated Results From CARTITUDE-2 Cohort A
British Journal of Haematology ; 197(SUPPL 1):34-35, 2022.
Article in English | EMBASE | ID: covidwho-1861221
ABSTRACT
Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell (CAR-T) therapy expressing two B-cell maturation antigen (BCMA)-targeting, singledomain antibodies. The multicohort, open-label, phase 2 CARTITUDE-2 study (NCT04133636) is evaluating ciltacel in patients (pts) with multiple myeloma (MM) in various clinical settings and assessing the suitability of outpatient administration. Updated results from CARTITUDE-2 cohort A are presented here. Cohort A pts had progressive MM after 1-3 prior lines of therapy (LOT;included proteasome inhibitor [PI] and immunomodulatory drug [IMiD]), were lenalidomide-refractory, and had no previous exposure to agents targeting BCMA. A single cilta-cel infusion at a target dose of 0.75 × 106 CAR+ viable T cells/kg was given 5-7 days after start of lymphodepletion (cyclophosphamide [300 mg/m2 ] and fludarabine [30 mg/m2 ] for 3 days). The primary endpoint was minimal residual disease (MRD) negativity at 10 -5 at any time point. Secondary endpoints were overall response rate (ORR), duration of response (DOR), time and duration of MRD negativity and adverse events (AEs). Response was assessed by International Myeloma Working Group criteria and AEs were graded by Common Terminology Criteria for Adverse Events version 5.0 (cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS] by American Society for Transplantation and Cellular Therapy). As of April 15, 2021 (median follow-up 9.7 months), 20 pts (65% men;median age 60 years [range 38-75]) received ciltacel, with 1 pt treated in an outpatient setting. Pts had a median of two prior LOT (range 1-3);60% with 1-2 prior LOT and 40% with three prior LOT. All pts were exposed to a PI, IMiD and dexamethasone;95% were exposed to alkylating agents and 65% to daratumumab. 95% of pts were refractory to last LOT;40% were triple-class refractory. ORR was 95% (95% CI 75.1-99.9);85% (95% CI 62.1-96.8) had ≥complete response (CR), and 95% (95% CI 75.1-99.9) had ≥very good partial response. The median time to first response was 1.0 months (range 0.7-3.3) and the median time to ≥CR was 2.6 months (range 0.9-7.9). The median DOR was not reached;progression-free survival (PFS) at 6 months was 90% (95% CI 65.6-97.4). Of MRD-evaluable pts ( n = 13), 92.3% (95% CI 64.0-99.8) were MRD-negative at 10 -5 . Haematological AEs (≥20% of pts) were neutropenia (95%;grade [gr] 3/4 95%), thrombocytopenia (80%;gr 3/4 35%), anaemia (75%;gr 3/4 45%), lymphopenia (65%;gr 3/4 60%) and leukopenia (55%;gr 3/4 55%). Ninety-five percent of pts had CRS (gr 3/4 10%);median time to onset was 7 days (range 5-9) and median duration was 4 days (range 2-11). Four pts (20%) had CAR-T neurotoxicity (all gr 1/2). Three pts (15%) had ICANS (all gr 1/2);median time to onset was 8 days (range 7-10) and median duration was 3 days (range 1-3). One pt had facial paralysis (gr 2) with time to onset of 29 days and duration of 51 days. No movement and neurocognitive treatment-emergent adverse events (TEAEs) occurred. One death occurred due to COVID-19 (assessed as treatment-related). Safety was manageable in the pt treated in an outpatient setting. Lenalidomide-refractory pts with MM and 1-3 prior LOT showed early and deep responses with a single cilta-cel infusion. No movement and neurocognitive TEAEs were reported, suggesting utilisation of successful monitoring and pt management strategies across phase 2/3 studies in the CARTITUDE program.
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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Cohort study / Observational study / Prognostic study Language: English Journal: British Journal of Haematology Year: 2022 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Cohort study / Observational study / Prognostic study Language: English Journal: British Journal of Haematology Year: 2022 Document Type: Article