CD3xCD20 Bispecific Antibodies Yields Long-Term Survival in Relapsed/Refractory B Cell Lymphoma: A Follow-up Study of Patients Treated in Pivotal Phase 1/2 Trials

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.618-618
• Main Authors: Kyvsgaard, Emil Ramsø, Clausen, Michael Roost, Hasselbalch Riley, Anna Caroline, Niemann, Carsten Utoft, Grønbæk, Kirsten, Hutchings, Martin, Husby, Simon
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-178323

Introduction: T-cell engaging CD3xCD20 bispecific antibodies like glofitamab, mosunetuzumab and epcoritamab are a new group of immunotherapies with promising results in B-cell lymphomas. T-cell engaging antibodies might have milder adverse effect profile compared to chimeric antigen receptor T-cell therapy (CAR-T). However, the duration of response to these new agents is still uncertain and follow-up times for glofitamab and epcoritamab have been short. We performed extensive follow-up of all patients in Denmark who received CD3xCD20 bispecific antibodies in early pivotal phase 1 / 2 trials to map the response, adverse effects and long-term survival, and baseline correlates with these outcomes. Methods: Patients who received T-cell engaging CD3xCD20 bispecific antibodies from 2017 to 2023 as part of a clinical trial were included. The patients' electronic health records were assessed for sex, age, prior therapy, dose received, stage of disease, response according to Lugano criteria, target lesion response, Cytokine Release Syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity (ICANS) events, infections leading to hospitalization, event-free and overall survival. Kaplan-Meier estimates were provided for all time-to-event end points. Hazard ratios with two-sided 95% confidence intervals were calculated from a Cox proportional-hazards model. Results: A total of 130 patients with relapsed/refractory B cell lymphoma who received bispecific CD3xCD20 antibodies were analyzed. The median age of patients was 70 years (21 to 87 years) and 58% were male. The median number of prior lines of therapy was 3 and the median Ann Arbor stage was 4. B-symptoms were present in 18% of patients before treatment. The median follow-up time from first treatment was 14.8 months (4 to 74 months). Best overall response rate in all patients was 75% (95% CI, 67-83); 54 patients (45%) had complete response (CR), and 37 patients (31%) had partial response (PR). Among patients with a complete response (CR), the median duration of response was 22.5 months and 29.4 months in patients with DLBCL and follicular lymphoma, respectively. Among all patients, the most common adverse effects included CRS (max. grade 1 n=45, max. grade 2 n=28, max. grade 3 n=3 max. grade 4-5 n=0), Varicella Zoster infections (n=8), hypogammaglobulinemia (n=14), therapy-related leukemia (n=3) and autoimmune colitis or hepatitis (n=5). Two patients were diagnosed with ICANS, both grade 1. A total of 54 patie