Zamtocabtagene Autoleucel Produces High ORR in Relapsed/Refractory DLBCL

Zamtocabtagene autoleucel produced “promising responses” in a phase 2 trial of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a presentation at the Tandem Meetings 2023.

Zamtocabtagene autoleucel is a chimeric antigen receptor (CAR) T-cell therapy targeting both CD19 and CD20. Fresh, not cryopreserved, zamtocabtagene autoleucel produced an overall response rate (ORR) of 82% in this trial.

The trial (ClinicalTrials.gov Identifier: NCT04792489) included 28 patients with relapsed/refractory DLBCL who had received at least 2 prior lines of treatment.


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The median age at baseline was 60 (range, 38-77) years, 61% of patients were men, and 50% had 2 or more extranodal sites. Most patients (79%) had received 2 prior lines of therapy, but 21% had received 3 or more. Fourteen percent of patients each had received a prior anti-CD19 antibody or polatuzumab.

Patients underwent leukapheresis within 7-14 days before receiving zamtocabtagene autoleucel. Lymphodepletion (with bendamustine or fludarabine and cyclophosphamide) occurred during the manufacturing process to facilitate a fresh infusion of CAR-T cells.

All 28 patients were treated, but 22 were evaluable per protocol. In the per-protocol population, the best ORR was 82%, with 10 complete responses (CRs) and 8 partial responses (PRs).

In all 28 patients, the best ORR was 79%, with 14 CRs and 8 PRs. Overall, there were 4 patients who had a PR that converted to a CR and 2 patients who had stable disease that converted to a PR.

“I think the responses here are very promising, showing that maybe dual targeting is a potential way to improve outcomes,” said study presenter Nirav N. Shah, MD, of the Medical College of Wisconsin in Milwaukee.

Dr Shah and colleagues are still trying to determine whether the use of dual targeting mitigates CD19 loss as a mechanism of resistance. He noted that, at the time of progressive disease, 2 patients had CD20 loss, and 1 patient had loss of CD19 and CD20.

The median follow-up was 10.3 months. The 6-month progression-free survival rate was 64% in the per-protocol population and 61% in all patients. There were 8 deaths on study, 6 due to progressive disease and 2 due to COVID-19.

Safety data were reported for all 28 patients. Neutropenia was seen in 23 patients (82%) up to day 28 and in 4 patients (14%) after day 28. Thrombocytopenia was seen in 7 patients (25%) up to day 28 and 2 patients (7%) thereafter.

There were no cases of grade 3 or higher cytokine release syndrome (CRS), 5 patients (18%) had grade 2 CRS, and 12 patients (43%) had grade 1 CRS. Two patients (7%) had grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), 3 patients (11%) had grade 2 ICANS, and 1 patient (4%) had grade 1 ICANS.

Disclosures: This research was supported by Miltenyi Biomedicine in collaboration with ICON plc. Dr Shah disclosed relationships with Legend Biotech, Ipsen-Epizyme, TG Therapeutics, Kite Pharma, Novartis, LOXO-Lilly, Janssen, Bristol Myers Squibb-Juno, Seattle Genetics, Miltenyi Biomedicine, Incyte, and Tundra Therapeutics.

Reference
Shah NN, Maziarz RT, Ghosh M, et al. Interim analysis of a phase II study of administered fresh bispecific anti-CD20/anti-CD19 CAR T-cell therapy – Zamtocabtagene autoleucel (zamto-cel) for relapsed/refractory (R/R) DLBCL (DALY II USA NCT04792489). Tandem Meetings 2023. February 15-19, 2023. Abstract 16.  

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