Infectious Complications in B-Cell Non-Hodgkin Lymphoma (NHL) Patients Treated with Bispecific Antibody Therapy (BsAb) As Compared to Chimeric Antigen Receptor T-Cell Therapy (CAR-T)

Background:

CAR-T has shown significant efficacy for relapsed or refractory NHL. However, its widespread use is limited by toxicities, manufacturing issues, and cost. BsAb is an off-the-shelf treatment option, with studies demonstrating high response rates but uncertain durability due to limited follow-up. We evaluated infectious complications associated with CAR-T compared to BsAb.

Methods:

We retrospectively evaluated the 18 NHL patients treated with odronextamab, a CD20xCD3 BsAb on clinical trial and not yet approved for NHL, at Beth Israel Deaconess Medical Center from 2015 to 2023. 8 odronextamab patients had prior CAR-T exposure, and 10 odronextamab patients did not; these cohorts were compared to each other. Then, 10 NHL patients treated with CAR-T alone were matched by age and number of prior lines of treatment to the 10 BsAb patients without prior CAR-T as an additional cohort comparison to BsAb alone. We evaluated clinical characteristics and infectious complications that occurred in the 12 months after initiation of BsAb in the odronextamab groups and after CAR-T in the matched cohort. Descriptive analysis was performed using R version 4.3 and one-way ANOVA.

Results:

Demographic data including age and number of prior lines of treatment, all-grade infections, grade ≥ 3 infections, viral, and fungal infections were similar between groups. The average number of all-grade infections per patient were 1.5, 1.9, and 1.2 for BsAb, BsAb + prior CAR-T, and CAR-T respectively (p=0.59), with a numerically greater proportion of bacterial infections for any CAR-T exposure (BsAb vs. CAR-T, p = 0.054; BsAb vs. BsAb + prior CAR-T, p = 0.18). Variables including proportion of time spent with Absolute Neutrophil Count<500, CD4<200, or Absolute Lymphocyte Count<500; grading of lymphopenia, neutropenia, anemia, or thrombocytopenia; hypogammaglobulinemia, and Cytokine Release Syndrome events were compared between groups. Combined CAR-T and BsAb exposure correlated with increased proportional time on study with CD4<200 compared to BsAb alone (0.88 vs 0.21, p=0.016). CAR-T exposure alone correlated with increased proportional time on study with severe neutropenia (0.03 vs. 0.00, p=0.021) and with CD4<200 (1.00 vs. 0.21, p=0.041) compared to BsAb alone.

Conclusion:

In this retrospective analysis, CAR-T exposure was associated with an increase in both the number of bacterial infections and the duration of immunologic compromise that may predispose NHL patients to infection compared to BsAB. These preliminary results will need to be confirmed within a larger BsAb and CAR-T cohort study, with multivariate analysis to determine risk factors for infection. These findings may ultimately help tailor the choices of anti-lymphoma therapy and infectious prophylaxis to the individual patient.

Alonso:Pfizer: Consultancy; Merck: Consultancy, Research Funding; Academy for Continued Healthcare Learning: Honoraria; AiCuris: Consultancy; Cidara Therapeutics: Consultancy; DSM-Firmenich: Consultancy; American Society of Health System Pharmacists and Clinical care options: Honoraria. Patell:Merck Research: Consultancy, Other: Personal fees. Arnason:BMS: Other: Speaker fees; Regeneron Pharmaceuticals, Inc.: Other: Speaker fees. von Keudell:Regeneron Pharmaceuticals, Inc.: Consultancy; Merck: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Genmab: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria.