Effects of a Dual-Targeting CD19/22 CAR T-Cell Therapy in Combination with Pembrolizumab for DLBCL

AUTO3 is a chimeric antigen receptor (CAR) T-cell targeting CD19/22 with limited duration of PD-1 blockade. A study presented at the 2020 ASH Annual Meeting found that AUTO3 in combination with pembrolizumab induced durable complete remissions (CRs) in patients with diffuse large B-cell lymphoma (DLBCL).

The phase I Alexander study included adult patients with relapsed/refractory or transformed DLBCL who had adequate organ function. AUTO3 was assessed at three dose levels: 50×106, 150×106, and 450×106. Patients received AUTO3 alone, with three doses of pembrolizumab 200 mg every three weeks starting on day 14 (regimen A), or with a single dose of pembrolizumab 200 mg on day one (regimen B).

As of July 13, 2020, 33 patients (median age, 59 years; range, 28-83 years) were treated with AUTO3. Patients had received a median of three prior therapies (range, 1-10 therapies), and most patients (79%) had refractory disease.

Treatment-related adverse events (AEs) included neutropenia (73%), thrombocytopenia (64%), anemia (61%), cytokine release syndrome (33%), pyrexia (30%), constipation (27%), and fatigue (24%). Most serious AEs were hematological or infectious and largely reversible, according to the authors. There were three cases (9%) of neurotoxicity/immune effector cell-associated neurotoxicity syndrome, all of which occurred during disease progression with very minimal to no CAR T-cells in the peripheral blood. These events were associated with confounding factors such as sepsis, metabolic acidosis, hyponatremia, and narcotic use.

Among 29 patients who had evaluable efficacy data, the overall response rate (ORR) was 69%, and the and CR rate was 52%. Almost all patients (n=14/15) who achieved CR did not experience relapse after a median follow-up of three months (range, 1-24 months). Among the 15 evaluable patients treated with AUTO3 >50×106 and pembrolizumab regimen B, the ORR was 73%, and the CR rate was 60%. No relapses occurred in patients who achieved a CR.


Ramakrishnan A, Ardeshna KM, Batlevi CL, et al. Phase 1 Alexander Study of AUTO3, the First CD19/22 Dual Targeting CAR T Cell Therapy, with Pembrolizumab in Patients with Relapsed/Refractory (r/r) DLBCL. Abstract 600. Presented at the 62nd American Society of Hematology Annual Meeting & Exposition, December 2-11, 2020.