The chimeric antigen receptor (CAR) T-cell therapy rapcabtagene autoleucel can elicit durable responses in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to phase 1 results presented at the 2022 ASH Annual Meeting.
For patients who received rapcabtagene autoleucel at the recommended phase 2 dose, the overall response rate was 83%, and the median duration of response was 16 months.
This trial (ClinicalTrials.gov Identifier: NCT03960840) included 47 patients with relapsed/refractory DLBCL. The median age at baseline was 65 years (range, 35-79), 21.3% of patients were refractory to all prior treatment lines, 27.7% had received 3 or more prior lines of therapy, and 29.8% had received a hematopoietic stem cell transplant.
Patients could receive bridging chemotherapy during the manufacture of rapcabtagene autoleucel, and 68.1% did so. After lymphodepletion with fludarabine and cyclophosphamide, patients received a single dose of rapcabtagene autoleucel at 1 of 4 dose levels — 2.5 x 106 CAR-T cells (n=4), 12.5 x 106 CAR- T cells (n=30), 25 x 106 CAR-T cells (n=7), or 40 x 106 CAR-T cells (n=6).
The median follow-up was 13 months. The complete response (CR) rate was 75% at the first dose level, 73% at the second dose level, 71% at the third dose level, and 67% at the fourth dose level. The overall response rate was 75%, 83%, 71%, and 67%, respectively.
The second dose level is the recommended phase 2 dose. Among patients who received this dose, the CR rate was 60% at 3 months, 62% at 6 months, 42% at 9 months, and 50% at 12 months. The median duration of response was 16 months.
Across all 4 dosing cohorts, all patients reported an adverse event (AE), and all but 2 patients reported a grade 3 or higher AE. Two patients had a dose-limiting AE. One was grade 4 cytokine release syndrome (CRS), and 1 was pancytopenia lasting more than 28 days after infusion.
CRS occurred in 16 patients. CRS was grade 1-2 in all but 2 patients. For patients who received the recommended phase 2 dose, the median time to CRS onset was 8 days, and the median time to resolution was 6 days. Three patients were admitted to the intensive care unit for CRS.
A total of 5 patients developed immune effector cell-associated neurotoxicity syndrome (ICANS), 3 of whom received the recommended phase 2 dose. The median time to ICANS onset and the median time to resolution of ICANS were both 16 days for this dose group.
A total of 14 patients died, but there were no deaths related to rapcabtagene autoleucel.
Disclosures: This research was supported by Novartis Pharmaceuticals. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Barba P, Kwon M, Briones J, et al. YTB323 (rapcabtagene autoleucel) demonstrates durable efficacy and a manageable safety profile in patients with relapsed/refractory diffuse large B-cell lymphoma: Phase I study update. Presented at ASH 2022. December 10-13, 2022. Abstract 439.