Mounzer Agha, MD, is the director of the Mario Lemieux Center for Blood Cancers at UPMC Hillman Cancer Center, and the clinical director of the Hematopoietic Stem Cell Transplantation of UPMC speaks about the ASCO 2021 – Abstract – CARTITUDE-2: Efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, in patients with progressive multiple myeloma (MM) after one to three prior lines of therapy.
Link to Abstract:
https://meetinglibrary.asco.org/record/195446/abstract
Background information:
Cilta-cel is a CAR T-cell treatment that expresses two single-domain antibodies that target BCMA and impart avidity. The multicohort, phase 2 CARTITUDE-2 research (NCT04133636) is assessing cilta-cel safety and effectiveness in a variety of therapeutic settings for patients with MM, as well as the feasibility of outpatient administration. The first results from Cohort A are shown here.
Methodologies:
Patients in Cohort A had progressed MM following 1–3 previous lines of treatment (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and had never been exposed to BCMA-targeting drugs. 5–7 days (d) following the initiation of lymphodepletion (daily cyclophosphamide [300 mg/m2] and fludarabine [30 mg/m2] for 3 days), a single cilta-cel infusion (target dose: 0.75106 CAR+ viable T cells/kg) was administered. Minimal residual disease (MRD) 10-5 negative was the major goal. Response rates (IMWG) and safety were secondary goals (per CTCAE; CRS and ICANS by ASTCT).
The following are the outcomes:
20 patients (65 percent male; median age 60 years [38–75]) got cilta-cel as of February 2021 data cutoff (median follow-up: 5.8 months [mo]; range: 2.5–9.8 mos); 1 patient was treated in an outpatient setting. Pts had a median of two prior LOT (1–3); 12 had three prior lines, and 8 had three previous LOT. All of the patients were given PI, IMiD, and dexamethasone, and 95 percent were given alkylating drugs and 65 percent were given daratumumab. The majority (95%) were refractory to the previous LOT, with 40% being triple refractory. The overall response rate was 95 percent (95 percent confidence interval: 75–100), with 75 percent (95 percent confidence interval: 51–91) achieving strict CR/CR and 85 percent (95 percent confidence interval: 62–97) achieving VGPR. The median time it took for the first reaction was 1.0 month (0.7–3.3), while the median time it took for the best response was 1.9 months (0.9–5.1). The median response time was not attained. At the data cutoff, all points (n = 4) with MRD-evaluable samples at 10-5 were MRD-negative. Neutropenia (95 percent; gr 3/4: 90 percent), thrombocytopenia (80 percent; gr 3/4: 35 percent), anemia (65 percent; gr 3/4: 40 percent), lymphopenia (60 percent; gr 3/4: 55 percent), and leukopenia (55 percent; all gr 3/4) were the hematologic AEs that accounted for 20% of the total. CRS was seen in 85 percent of patients, with 10% of them being grade 3/4. CRS onset took an average of 7 days (5–9), with a median length of 3.5 days (2–11). CAR T-cell neurotoxicity was observed in 20% of patients (all grades 1/2). ICANS was found in three patients (1 gr 1; 2 gr 2), with a median starting time of 8 days (7–11) and a median duration of 2 days (1–2). One patient experienced grade 2 facial paralysis, which lasted 51 days from the time of commencement. One person died as a result of COVID-19 (the cause of death was determined to be treatment-related by the investigator). The patient’s safety profile was tolerable in an outpatient environment.
Final Thoughts:
In patients with MM who had had 1–3 previous LOT, a single cilta-cel infusion at the indicated phase 2 dosage resulted in early and profound responses with a tolerable safety profile. Outpatient tx will be considered suitable in this and other CARTITUDE-2 cohorts, as well as the CARTITUDE-4 research, based on updated effectiveness and safety data.