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Gastrointestinal Adverse Events Observed After Chimeric Antigen Receptor T-Cell Therapy

Abu-Sbeih, Hamzah MD*; Tang, Tenglong MD*,†; Ali, Faisal S. MD*; Luo, Wenyi MD; Neelapu, Sattva S. MD§; Westin, Jason R. MD, MS§; Okhuysen, Pablo C. MD; Foo, Wai Chin MD; Curry, Jonathan L. MD; Richards, David M. MD*; Ge, Phillip S. MD*; Wang, Yinghong MD, PhD*

American Journal of Clinical Oncology: October 2019 - Volume 42 - Issue 10 - p 789–796
doi: 10.1097/COC.0000000000000596
Original Articles: Experimental Therapeutics
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Background: Chimeric antigen receptor T-cell (CART) therapy can significantly improve outcomes for patients with certain hematologic malignancies. The most notable drawbacks of CART are cytokine release syndrome and CART-related encephalopathy syndrome. Gastrointestinal adverse events (GI-AEs) have not yet been reported in association with CART. Herein, we describe the incidence and clinical features of GI-AEs observed after CART.

Materials and Methods: We report a case series of patients with hematologic malignancies who received CART, in a clinical trial or as the standard of care, and subsequently suffered from GI-AEs between 2012 and 2018.

Results: In our cohort, 37 of 132 (28%) patients experienced GI-AEs. All 37 experienced diarrhea with a median onset of 7 days (interquartile range, 4 to 25 d) after CART infusion. The median age of these patients was 58 years. Most had diffuse large B-cell lymphoma (51%). Seventeen patients experienced cytokine release syndrome, and 9 experienced CART-related encephalopathy syndrome. The interleukin-6 antagonist was required in 15 patients. Overall, 49% of patients had grade 1 diarrhea, 32% had grade 2, and 15% had grade 3. Other gastrointestinal symptoms in these patients were abdominal pain (41%), nausea and vomiting (49%), fever (8%), bloody stools (3%), and abdominal distension (5%). The median duration of symptoms was 6 days (interquartile range, 3 to 9 d). In 32 patients who underwent imaging, 8 (25%) had findings suggestive of gastrointestinal tract inflammation. Nine (24%) patients experienced GI-AE recurrence after initial improvement. The symptoms were attributed to an alternative cause in 17 (13%) cases and to CART in 20 (15%) cases. One patient developed CART-related refractory colitis that eventually responded to antibiotics for pneumonia.

Conclusion: CART-related GI-AEs occur in 15% of patients treated with CART. These symptoms are typically mild and self-limiting, requiring only symptomatic treatment. Nevertheless, CART may, in rare cases, lead to refractory colitis.

Departments of *Gastroenterology, Hepatology, and Nutrition

Pathology

§Lymphoma and Myeloma

Infectious Diseases, Infection Control & Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX

Minimally Invasive Surgery Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China

H.A.-S. and T.T. are cofirst authors.

The ethics approval of this study was granted by the Institutional Review Board committee at The University of Texas MD Anderson Cancer Center (PA18-0472). Consent was waived for this study. Y.W.: was the senior author of this study, developed the concept, designed the study, interpreted the results, ensured that the accuracy and integrity of the data was preserved at all stages, agreed to be accountable for all aspects of this study, was in charge of the overall direction and planning of the study, and contributed to the writing of the manuscript with input from all authors. H.A.-S. and T.T.: collected the data for the study, helped conduct and interpret the analysis, and wrote the manuscript. F.S.A.: assisted in writing and editing the paper and collecting data from patients’ medical charts. W.L. and W.C.F.: provided pathologic images and contributed to the pathologic descriptions. S.S.N., D.M.R., P.S.G., J.R.W., P.C.O., and J.L.C.: critically revised the final version of the manuscript. All authors read and approved the final manuscript.

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

The authors declare no conflicts of interest.

Reprints: Yinghong Wang, MD, PhD, Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1466, Houston, TX 77030. E-mail: ywang59@mdanderson.org.

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