925. Infectious Complications Following Chimeric Antigen Receptor (CAR) T-cell Therapy
Authors: Trottier Caitlin , Larsen Christian , Bindal Poorva , Dodge Laura E , Elavalakanar Pavania , Knudsen Elisabeth , Kim Sirwoo , Logan Emma , Urman Arielle R , Frigault Matthew , Fishman Jay A , Fishman Jay A , Arnason Jon , Alonso Carolyn D 
Published: December 2021

Abstract

Background
Chimeric antigen receptor (CAR-T) T-cell therapy is a novel immunotherapy for cancer treatment in which patients are treated with targeted, genetically-modified T-cells. Common side effects include cytokine release syndrome, neurotoxicity, hypogammaglobulinemia, and increased susceptibility to infections. Long-term infectious outcomes are poorly characterized.

Methods
We retrospectively examined patients who received CAR-T therapy at BIDMC & MGH from July 2016 to March 2020 and evaluated bacterial, fungal, viral, and parasitic infections at 3 months intervals to 1 year following cell infusion. The incidence, timing, and outcomes of the infectious complications were evaluated.

Results
In total, there were 47 patients; averaging 61.4 years of age (±12 years). Primary indications for CAR-T therapy included diffuse large b-cell lymphoma (65%) and multiple myeloma (25%), chronic lymphocytic leukemia (2%) and mantle cell lymphoma (2%). Patients had received an average 4 ± 2.9 lines of chemotherapy prior to CAR-T infusion; 19 subjects (40%) had a history of prior autologous stem cell transplant. All patients received acyclovir for antiviral prophylaxis and most received either trimethoprim-sulfamethoxazole (24/47; 51%) or atovaquone (16/47; 34%) for pneumocystis prophylaxis. In the first year, 35/47 (74.5%) of subjects experienced at least one infection with an infection rate of 84.4/10,000 person days. Median time to first infection was 59 days (range 1-338 patient days). 31/47 (66.0%) subjects had at least one bacterial infection, with pulmonary (42/113; 37.2%) sources being the most common site of infection. 13/47 (27.7%) of patients had a viral infection (predominantly respiratory viral infections) and 6/47 (12.8%) had a proven or probable fungal infection. Death attributed to infection was noted in 2 subjects (4.3%), both related to COVID-19. Baseline IgG levels were significantly lower in the group with infections (p=0.028), while white blood cell count and absolute neutrophil counts were comparable.
Table 1. Baseline Demographic, Clinical Characteristics, and Outcomes of 47 Recipients of CAR-T Cell Therapy by Infection Status

Notes
BMI: body mass index; DLBCL: diffuse large B-cell lymphoma; CLL: chronic lymphocytic leukemia; Flu/Cy: Fludarabine/cyclophosphamide; IVIG: intravenous immunoglobulin; WBC: white blood cell count; ANC: absolute neutrophil count; ALC: absolute lymphocyte count.
Table 2. Characteristics of the 113 Infections in the 35 Subjects Who Developed Infections

Conclusion
Infectious complications, particularly of bacterial etiology, are common in the first year following CAR-T therapy. These data may inform future prophylactic strategies in this patient population.

Disclosures
Matthew Frigault, MD, Arcellx (Consultant)BMS (Consultant)Iovance (Consultant)Kite (Consultant)Novartis (Consultant) Jay A. Fishman, MD, Nothing to disclose Jon Arnason, MD, BMS/Juno (Advisor or Review Panel member)Regeneron (Advisor or Review Panel member)