Impact of pre-existing autoimmune disease on clinical outcomes in patients treated with bispecific monoclonal antibodies for B-cell lymphomas.

Abstract

e19008 Background: Bispecific antibodies (BsAbs), including glofitamab, epcoritamab, and mosunetuzumab, are FDA-approved for relapsed/refractory B-cell lymphomas. Patients with pre-existing autoimmune disease (AD) were excluded from pivotal trials, resulting in limited real-world data on outcomes in this population. We evaluated the impact of pre-existing AD on clinical outcomes in patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) treated with BsAbs. Methods: We performed a multicenter retrospective cohort study using the TriNetX database. Two cohorts were identified: patients with FL or DLBCL and a documented pre-existing AD treated with BsAbs, and a comparator cohort without AD treated with BsAbs. Patients were matched 1:1 using propensity score matching based on age, sex, race, comorbidities, prior CAR T-cell therapy, and baseline laboratory values. Outcomes included 1-year and 3-year overall survival (OS); cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) within 60 days; and infections, neutropenia, and ICU admissions within 90 days of BsAb initiation. Survival was assessed using Kaplan–Meier analysis, and outcomes were summarized using hazard ratios (HR), risk ratios (RR), and 95% confidence intervals (CI). Results: In the unmatched cohorts, 257 patients had a pre-existing AD and 631 patients comprised the non-AD control group. Following propensity score matching, 228 patients were included in each cohort. There was no statistically significant difference in one-year or three-year OS between patients with pre-existing AD and those without AD (1-year HR = 0.85 [95% CI, 0.62–1.18]; 3-year HR = 0.93 [95% CI, 0.69–1.26]). Rates of CRS (RR = 1.13 [95% CI, 0.87–1.46]) and ICANS (RR = 1.00 [95% CI, 0.64–1.58]) within 60 days were similar between cohorts. Infection rates (RR = 1.14 [95% CI, 0.91–1.43]) and ICU admissions (RR = 1.09 [95% CI, 0.71–1.65]) within 90 days did not significantly differ. Patients with pre-existing AD had a higher risk of neutropenia within 90 days compared with those without AD (RR = 1.26 [95% CI, 1.04–1.52]). Conclusions: In this large real-world analysis pre-existing autoimmune disease was not associated with inferior overall survival or increased rates of CRS, ICANS, infection, or ICU admission in patients with relapsed/refractory FL or DLBCL. Pre-existing AD was associated with a higher risk of neutropenia, underscoring the importance of close hematologic monitoring. Outcome Pre-Existing AD(n= 228) No-AD(n=228) HR/RR [95% CI] 1-year OS 63.4% 57.9% 0.85 [0.62-1.18] 3-year OS 44.5% 45.6% 0.93 [0.69-1.26] CRS (≤60 days) 35.1% 31.1% 1.13 [0.87-1.46] ICANS (≤60 days) 14.0% 14.0% 1.00 [0.64-1.58] Infection (≤90 days) 42.5% 37.3% 1.14 [0.91-1.43] Neutropenia (≤90 days) 53.9% 43.0 1.26 [1.04-1.52] ICU Admission (≤90 days) 16.7% 15.4% 1.09 [0.71-1.65]