Introduction:NHL treatment with anti-CD20 antibodies is associated with an increased risk of infections. Mosunetuzumab (mosun) is a novel anti-CD20xCD3 BsAb that has been examined in clinical trials for different NHL subtypes and was recently approved for treating R/R follicular lymphoma. While the open-label clinical trial of mosun reported that 17% of the patients experienced infectious complications, a detailed analysis of the incidence and types of infections in patients receiving this treatment has not been reported.

Methods: This is a single-center, IRB-approved, retrospective analysis of patients with R/R NHL receiving mosun, either on a study protocol (NCT02500407) at the recommended phase 2 dose or as commercial use. Patients who completed at least 1 treatment cycle and had at least 30 days of follow-up were included in this analysis. Patient demographics, information on the lymphoma, and infection variables were collected by chart review. All infection-specific variables were collected from the start of mosun therapy until the initiation of the next line of therapy or the last follow-up, whichever came first. The data cut-off was on 7/22/23. Infectious events were graded according to common terminology criteria for adverse events (CTCAE) version 5.0. Baseline characteristics were analyzed for infection risk by performing a Cox regression analysis.

Results: Between October 2016 and July 2023, 48 patients were treated with mosun at our center, and 44 met the study inclusion criteria. Four patients had only received one dose or did not have sufficient follow at the time of the analysis. Baseline characteristics are summarized in Table 1. After a median follow-up of 6.8 months (range 0.7-59.7), we recorded 37 infection episodes in 16/44 patients (36.4%). Amongst these, the frequencies of viral, bacterial, and fungal infections were 54.1% (20/37), 43.2% (16/37), and 2.7% (1/37), respectively. The most common infection types were upper respiratory tract infections 42.1% (20/37), skin and soft tissue infections16.2% (6/37), including 3 shingles episodes), genitourinary infections 10.8% (4/37), and lower respiratory tract infections 10.8% (4/37). Of all the infections, 9/37 (24.3%) were Grade 3 or higher; of these, 2/37 (5.4%) were Grade 5 (1 biliary sepsis, 1 COVID pneumonia). The cumulative incidence of infection was 25% over the follow-up period (figure 1). The median time to the first infection was 144 days (range 29-1821). Among the patients who experienced infections, the infection rate was 1.54 every 100 days at risk within the first three months. The infection rate was 1.69 every 100 days at risk between three and six months and 0.37 every 100 days at risk beyond six months for patients with infection. We evaluated the type of lymphoma (i.e., aggressive vs. indolent), patients' age, number of prior therapies before BsAb administration, prior CAR-T therapy, prior autologous SCT, baseline hypogammaglobulinemia, and baseline cytopenia's as risk factors of infection with a univariate Cox regression analysis. We found that none of these characteristics were associated with the risk of infection with statistical significance. However, in a multivariate Cox regression analysis, patients who received CAR-T therapy before starting a BsAb were at a slightly higher risk of developing an infection (OR = 6.13; 95% CI: 0.90, 41.74, p = 0.063).

Conclusion: Infection risk in patients with R/R NHL treated with mosun either on protocol or for commercial use appears to be higher than in the clinical trial experience reported in the literature. Viral infections were especially common, including respiratory infections and shingles episodes. Our findings highlight the need for careful monitoring and implementation of preventive strategies to decrease the infection burden in these vulnerable patients.

Epstein-Peterson:Viracta: Research Funding; WebMD: Honoraria; Amgen: Research Funding; OncLive: Honoraria; Kymera: Research Funding. Ghione:Secura Bio: Consultancy; Kyowa Hakko Kirin: Consultancy; AstraZeneca Pharmaceuticals: Consultancy; Kite, A Gilead Company: Research Funding. Hamlin:ADC Therapeutics: Consultancy. Horwitz:Seattle Genetics: Research Funding; ONO Pharmaceuticals: Consultancy; Abcuro Inc.: Consultancy; Yingli Pharma Limited: Consultancy; Shoreline Biosciences, Inc.: Consultancy; Cimieo Therapeutics: Consultancy; Takeda: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Kyowa Hakko Kirin: Consultancy, Research Funding; Tubulis: Consultancy; ADC Therapeutics: Research Funding; Trillium Therapeutics: Consultancy, Research Funding; Affimed: Research Funding; Celgene: Research Funding; Crispr Therapeutics: Research Funding; Auxilius Pharma: Consultancy; Verastem/SecuraBio: Research Funding; SecuraBio: Consultancy; Millenium: Research Funding. Johnson:Myeloid Therapeutics: Consultancy. Kumar:Seattle Genetics: Research Funding; Adaptive Biotechnologies: Research Funding; Loxo/Lily Oncology: Consultancy, Research Funding; Pharmacyclics: Research Funding; Kite Pharma: Consultancy; Janssen: Consultancy; Astra Zeneca: Consultancy, Research Funding; Abbvie Pharmaceuticals: Research Funding; Genentech: Consultancy, Research Funding; Celgene: Research Funding; BridgeBio: Current equity holder in publicly-traded company; Beigene: Research Funding. Moskowitz:Seattle Genetics: Honoraria, Research Funding; ADC Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Beigene: Research Funding; Merck: Honoraria, Research Funding; Incyte: Research Funding. Palomba:Cellectar: Honoraria; Pluto Immunotherapeutics: Honoraria; GarudaTherapeutics: Honoraria; Kite: Honoraria; Novartis: Honoraria; Smart Immune: Honoraria; Juno: Honoraria, Patents & Royalties; Ceramedix: Honoraria; Rheos: Honoraria; Thymofox: Honoraria; Seres Therapeutics: Honoraria, Patents & Royalties; MustangBio: Honoraria; BMS: Honoraria; Synthekine: Honoraria. Torka:ADC Therapeutics: Consultancy; TG Therapeutics: Consultancy; Seagen: Consultancy; Genentech: Consultancy; Lilly USA: Consultancy; Genmab: Consultancy. Vardhana:Koch Disruptive Technologies: Consultancy; Immunai: Consultancy. Zelenetz:Pharmacyclics: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; SAB: Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; None other than mutual funds (401K): Current equity holder in publicly-traded company; Abbvie: Research Funding; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; MEI Pharma Inc: Consultancy, Honoraria, Research Funding. Salles:BeiGene: Consultancy; BMS/Celgene: Consultancy; Kite/Gilead: Consultancy; Genmab: Consultancy; Nurix: Consultancy; AbbVie: Consultancy, Honoraria; ATB Therapeutics: Consultancy; Ipsen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Novartis: Consultancy; Molecular Partners: Consultancy; Orna: Consultancy; Loxo/Lilly: Consultancy; Merck: Consultancy, Honoraria; Incyte: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Debiopharm: Consultancy; EPIZYME: Consultancy; Nordic Nanovector: Consultancy; Owkin: Current holder of stock options in a privately-held company. Falchi:Genmab: Consultancy, Research Funding; Abbvie: Consultancy, Other: Advisory Board, Research Funding; Genentech: Consultancy, Other: Advisory Board, Research Funding; Roche: Consultancy, Research Funding; Seagen: Other: Advisory Board; ADC Therapeutics: Other: Advisory Board; AstraZeneca: Consultancy.

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