Cema-Cel Shows Durable Response in Relapsed or Refractory LBCL

Cemacabtagene ansegedleucel (cema-cel) showed durable response rates and manageable safety in patients with CD19 chimeric antigen receptor (CAR) T-cell naïve, relapsed or refractory large B-cell lymphoma (LBCL), according to the ALPHA2/ALPHA studies published in the Journal of Clinical Oncology. These results support further evaluation of the CD19 CAR T-cell therapy.

The phase 1 trials led by Frederick Locke, MD, of Moffitt Cancer Center, evaluated the safety and efficacy of cema-cel and its predecessor, ALLO-501, in 33 CAR T-naïve patients (median age, 66) with a median of three prior therapies. The primary objective was to determine the maximum tolerated dose and phase 2 dose regimen of cema-cel with ALLO-647, an anti-CD52 monoclonal antibody. Secondary objectives include safety, as measured by adverse events, and efficacy as measured by overall response rate (ORR)

Prior to cema-cel infusion, patients received a lymphodepletion regimen of fludarabine (30 mg/m² once daily) and cyclophosphamide (300 or 500 mg/m² once daily) for 3 days plus escalating doses of ALLO-647.

Patients in the single-dose cohorts received a single cema-cel dose at 120 × 10⁶ CAR+ cells. If patients in the consolidation cohorts achieved a complete response (CR), partial response, or stable disease at day 28, they were eligible for an additional cema-cel dose on day 30 after receiving ALLO-647 on day 29. The median follow-up was 10.1 months.

Dr. Locke and colleagues reported an ORR of 58%, a CR rate of 42%, and a median overall survival of 14.4 months. CAR-T expansion was observed following infusion, and the median duration of response was 23.1 months in those who achieved a CR. The median progression-free survival was 3.9 months for the overall population, and 24.0 months for patients who achieved a CR.

The researchers also reported a tolerable safety profile. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 94% of patients, most commonly neutropenia (82%), anemia (46%), thrombocytopenia (42%), lymphopenia (33%), and decreased white blood cell count (30%). Serious TEAEs occurred in 42% of patients, most commonly infusion-related reactions to ALLO-647 (6%), pyrexia (6%), bacteremia (6%), cytomegalovirus reactivation (6%), pneumonia (6%), and COVID-19 (6%).

The researchers did not observe any dose-limiting toxicities or cases of graft-versus-host disease, immune effector cell–associated neurotoxicity syndrome, or grade 3 or higher cytokine release syndrome.

“As an off-the-shelf treatment with a safety profile that is compatible with outpatient management and a preliminary efficacy profile in R/R LBCL that is similar to available autologous therapies, a clinically meaningful improvement in relapse prevention, measured in ALPHA3 by event-free survival, could fundamentally alter the front-line treatment paradigm for newly diagnosed LBCL,” wrote Dr. Locke and colleagues.