EFFICACY AND SAFETY OF CILTACABTAGENE AUTOLEUCEL (CILTA-CEL), A BCMA-DIRECTED CAR-T CELL THERAPY, IN PATIENTS WITH PROGRESSIVE MULTIPLE MYELOMA (MM) AFTER 1–3 PRIOR LINES OF THERAPY: CARTITUDE-2 PHASE 2 STUDY
Hematology, Transfusion and Cell Therapy
; 43:S255, 2021.
Article
in English
| EMBASE | ID: covidwho-1859623
ABSTRACT
Objectives:
Cilta-cel is a CAR-T cell therapy that expresses 2 BCMA-targeting single-domain antibodies, designed to confer avidity. In the multicohort, phase 2 CARTITUDE-2 study (NCT04133636), the safety and efficacy of cilta-cel in various clinical settings and suitability of outpatient administration was explored in patients with multiple myeloma. Material andmethods:
Patients enrolled in Cohort A had progressive MM after 1–3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and were naïve to BCMA-targeting agents. A single cilta-cel infusion (target dose 0.75 × 106 CAR+ viable T cells/kg) was given 5–7 days after start of lymphodepletion (daily cyclophosphamide [300 mg/m2] and fludarabine [30 mg/m2] for 3 days). The primary outcome was minimal residual disease (MRD) 10-5 negativity. Secondary outcomes were response rates (per IMWG criteria) and safety (per CTCAE;CRS and ICANS by ASTCT).Results:
As of the February 2021 data cutoff (median follow-up 5.8 months [2.5–9.8]), 20 patients (65% male;median age 60 years [38–75]) received cilta-cel;1 patient was treated in an outpatient setting. Patients (n = 12 <3 prior LOT;n = 8 3 prior LOT) received a median of 2 (1–3) prior LOT. All patients were exposed to PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab. The majority (95%) were refractory to the last LOT;40% were triple-class refractory. Overall response rate was 95% (95% CI 75–100), 75% (95% CI 51–91) achieved stringent CR/CR, and 85% (95% CI 62–97) achieved ≥VGPR. Median time to first response was 1.0 month (0.7–3.3);median time to best response was 1.9 month (0.9–5.1). Median duration of response was not reached. All patients (n = 4) with MRD-evaluable samples at 10-5 at data cutoff were MRD-negative. Hematologic AEs ≥20% were neutropenia (95%;grade 3/4 90%), thrombocytopenia (80%;grade 3/4 35%), anemia (65%;grade 3/4 40%), lymphopenia (60%;grade 3/4 55%), and leukopenia (55%;all grade 3/4). 85% of patients had CRS;10% were grade 3/4. Median time to CRS onset was 7 days (5–9), with a median duration of 3.5 days (2–11). CAR-T cell neurotoxicity occurred in 20% of patients (all grade 1/2). Three patients had ICANS (n = 1 grade 1;n = 2 grade 2);median time to onset was 8 days (7–11) and median duration was 2 days (1–2). One patient had grade 2 facial paralysis;time to onset was 29 days with a duration of 51 days. One death occurred due to Covid-19 (assessed as treatment-related by investigator). The safety profile was manageable in the patient who was treated in an outpatient setting.Discussion:
Updated efficacy and safety findings will inform suitability of outpatient treatment in this and other cohorts of CARTITUDE-2 as well as the CARTITUDE-4 study.Conclusion:
A single cilta-cel infusion at the recommended phase 2 dose led to early and deep responses with a manageable safety profile in patients with MM who had 1–3 prior LOT.
ciltacabtagene autoleucel; cyclophosphamide; daratumumab; dexamethasone; fludarabine; immunomodulating agent; lenalidomide; proteasome inhibitor; adult; anemia; cancer patient; cancer resistance; case report; chimeric antigen receptor T-cell; clinical article; clinical trial; cohort analysis; conference abstract; coronavirus disease 2019; drug combination; drug safety; drug therapy; facial nerve paralysis; female; follow up; human; human tissue; leukopenia; lymphocytopenia; male; middle aged; minimal residual disease; multiple myeloma; neurotoxicity; neutropenia; outcome assessment; outpatient; overall response rate; phase 2 clinical trial; T lymphocyte; thrombocytopenia
Full text:
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Hematology, Transfusion and Cell Therapy
Year:
2021
Document Type:
Article
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