Infectious complications of CD20 x CD3 bispecific antibody therapy in patients with B-cell lymphoma.

Abstract

e24116 Background: CD20 x CD3 bispecific antibody therapies (BsAbs) are currently approved for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and are under evaluation in multiple B-cell histologies. While cytokine release syndrome and neurotoxicity are notable toxicities, the frequency and severity of infections are less well understood, as are the clinical factors associated with risk of infection. We sought to describe our single-institution experience with infectious complications associated with BsAbs in B-cell lymphoma. Methods: We conducted an IRB-approved, retrospective comprehensive chart review at our NCI-designated comprehensive cancer center of all patients age > = 18y treated with at least one dose of CD20 x CD3 BsAb for a diagnosis of B-cell lymphoma between 1/10/2020-7/15/2024. All infections occurring within 18 months of initiation of therapy were identified and graded according to CTCAE v.5. We collected key demographic and clinical features, including quantitative serum immunoglobulin levels, use of antimicrobial prophylaxis, and use of intravenous immunoglobulin (IVIG). Results: 27 consecutive patients treated with BsAb were identified (median age 65, 63% male). The patients had median ECOG PS of 1, and 3 chronic comorbid conditions, with the most common being hypertension, hypercholesterolemia, and malnutrition. Histologies treated included DLBCL (n = 16), FL (n = 4), marginal zone lymphoma (n = 3), mantle cell lymphoma (n = 1), and B-cell lymphoma NOS (n = 3), with a median of 3 prior lines of therapy. Patients were treated with mosunetuzumab (n = 12), glofitamab (n = 10), and epcoritamab (n = 5). Most common antimicrobial prophylaxes were acyclovir (100%), SMX/TMP (89%), and fluconazole (42%). Gram positive bacterial infection occurred in 9 pts (33%); 4/9 were grade 2, 3/9 grade 3, and 2/9 grade 5. New-onset hypogammaglobinemia occurred in 8 pts (30%). Of these, only 3 patients received pre-emptive IVIG, and 3/8 pts subsequently developed grade 3+ infection. Neutropenic fever occurred in 6/27 pts (22%), four grade 4 and two grade 5. Candidiasis occurred in 3/27 pts (11%), two grade 2 and one grade 5; one of these three pts had received prophylactic fluconazole. Gram negative bacterial infection occurred in 4/27 pts (15%), all grade 5. COVID-19 infection occurred in 4/27 pts (15%), one grade 2 and three grade 3. Conclusions: CD20xCD3 therapy was associated with high rates of severe or fatal infection in this single-institution real world study. Greater consideration to preemptive IVIG and antimicrobial prophylaxis may be warranted with such therapy, and further studies to characterize individual risk and optimal management strategies are needed.