Treatment of large B-cell lymphomas using lisocabtagene maraleucel (liso-cel) was associated with clinically meaningful activity and a low incidence of grade 3 or higher cytokine release syndrome (CRS) or neurotoxicity in the TRANSCEND NHL 001 clinical trial, the results of which were published in The Lancet

In this multicenter, seamless design study (ClinicalTrials.gov Identifier: NCT02631044), patients with relapsed/refractory large B-cell lymphomas received liso-cel at varying dosage levels. These levels were 50 x 10⁶ CAR⁺ T cells for level 1 (45 patients), 50 x 10⁶ CAR⁺ T cells in 2 doses for dosage level 1 (6 patients), 100 x 10⁶ CAR⁺ T cells for level 2 (177 patients), and 150 x 10⁶ CAR⁺ T cells for level 3 (41 patients). The primary study endpoints were the objective response rate, incidence of adverse events, and dose-limiting toxicities. Secondary endpoints included the number of patients who achieved a complete response, duration of response, progression-free survival, overall survival, and cellular kinetic variables.

A total of 269 patients (median age, 63 years; 65% men) received 1 or more doses of liso-cel. The median number of prior systemic therapies was 3 (interquartile range, 2-4), and chemotherapy-refractory disease was present in 67% of treated patients. In addition, 44% of patients had never achieved a complete response with previous treatment.

Efficacy was evaluable in 256 patients. The objective response rate was 73% (95% CI, 66.8-78.0); 53% (95% CI, 46.8-59.4) of patients showed a complete response.

The level 2 dose of 100 x 10⁶ CAR⁺ T cells was recommended for the dose-confirmation study phase, based on a comparison of objective response rate and low-grade CRS rates across dosage levels.

The rate of CRS was 42%, with 2% of patients having grade 3 or higher CRS. Adverse neurological events occurred in 30% of patients, with 10% of patients having grade 3 or higher neurological events. Grade 3 or worse neutropenia (60%), anemia (37%), and thrombocytopenia (27%) were the most common adverse events reported.

Dose-limiting toxicities were reported in 6% of patients. A total of 7 fatalities occurred in patients who had treatment-emergent adverse events. One of the deaths was considered related to a dose-limiting toxicity, which was diffuse alveolar damage at a level-1 dosage.

“In summary, findings of the TRANSCEND trial show that liso-cel can lead to rapid and durable remission, with low incidence of all-grade and severe cytokine release syndrome and neurological events among patients with high-risk aggressive relapsed or refractory large B-cell lymphomas,” wrote the study investigators.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.