1098. Norovirus Infection in Cancer Patients Undergoing Chimeric Antigen Receptor T-cell Immunotherapy (CAR-T)

Abstract

BackgroundCAR-T is used to treat certain refractory hematological malignancies. B-cell aplasia and immunosuppression used to treat CAR-T side effects increase infection risk. Little data are available describing Norovirus (NoV) infections in CAR-T recipients.MethodsWe reviewed the medical records of 134 patients with NoV diarrhea (identified by nucleic acid amplification test) between 2016-2019. Of these patients, nine received CAR-T prior to developing NoV. Here we describe their demographics, clinical characteristics, treatments, and complications.ResultsThe median age was 49 years (Table 1). Patients’ underlying malignancies included Non-Hodgkin’s Lymphoma (4), Acute Lymphoblastic Leukemia (3), Chronic Lymphocytic Leukemia (1) and metastatic Sarcoma (1). Prior to development of NoV, six patients had undergone hematopoietic stem cell transplant, and 1 had received checkpoint inhibitor therapy. Five patients experienced cytokine release syndrome after CAR-T, and 1 experienced CAR-T-related encephalopathy syndrome (Table 2). Two patients received interleukin-6 antagonist therapy, and one received high dose steroids. Time to diarrhea onset post-CAR-T cell infusion was variable(median 256days, IQR 26-523 days).Six had an absolute lymphocyte count< 1000/mm3 at diarrhea onset. Three had diarrhea for >14 days; median diarrhea duration in the other 6 patients was 4 days. Other GI complaints included abdominal pain (3), nausea (4), and vomiting (3). For NoV treatment, three received oral immunoglobulin, and 8 received Nitazoxanide. Complications included development of concomitant GI-GVHD(5), ileus (2), need for TPN (3), renal failure requiring dialysis (2), ICU stay (3), and death (2). Two patients were co-infected with other enteropathogens such as rotavirus, enteropathogenic and enteroaggregative E.Coli and Clostridioides difficile. Three patients with diarrhea lasting >14 days had serial samples collected over time; NoV shedding lasted 81-546 days. NoV was genotyped in 6 patients(Table 3) and included GII.2(2), GII.4(2), GII.6(1) and GII.12(1).Table 1: Patient characteristics (N=9) Table 2: CAR-T related factors Table 3: NoV Genotypes ConclusionNoV belonging to various genotypes is an important cause of acute and chronic diarrhea in patients receiving CAR-T cell therapy.Disclosures Adilene Olvera, MPH MLS (ASCP), MERK (Grant/Research Support, Scientific Research Study Investigator) Robert L. Atmar, MD, Takeda Vaccines, Inc. (Grant/Research Support) Mary K. Estes, PhD, Takeda Vaccines (Consultant, Grant/Research Support)