Outcomes of CD19 Chimeric Antigen Receptor T Cell Therapy in Patients with Gastrointestinal Tract Involvement of Large B Cell Lymphoma.

Abstract

CD19-directed chimeric antigen receptor (CAR) T cell therapy with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) is approved for the standard of care treatment of relapsed or refractory large B cell lymphoma (LBCL). Patients with LBCL involving the gastrointestinal (GI) tract are at risk of perforation after lymphoma-directed therapy. The outcomes of CAR T cell therapy in patients with GI involvement have not been reported previously. This study aimed to determine the safety and efficacy of CD19 CAR T cell therapy in patients with LBCL involvement of the GI tract. This was a single-center retrospective study of 130 consecutive patients treated with standard of care or expanded-access axi-cel or tisa-cel for LBCL. Twenty-four of these patients had radiologic involvement of the GI tract before CAR T infusion. Incidence rates of severe immune effector cell-mediated toxicities and clinical outcomes were compared between the GI involvement and non-GI involvement groups. Three of the 24 patients with GI tract involvement experienced perforation. One patient had a contained gastric perforation after leukapheresis while receiving bridging radiation therapy to the stomach. This patient was eventually able to proceed with lymphodepletion and product infusion. In the other 2 patients, GI tract perforation occurred at day +13 and day +35 after CAR T infusion. All 3 patients subsequently died while experiencing lymphoma progression. Upper GI bleeding occurred in 1 other patient in the context of progressive disease at 6 months after product infusion. The incidence rates of severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, length of hospital stay, and use of anti-IL-6 and steroids were similar in the 24 patients with GI tract involvement and the 106 patients without GI tract involvement. No significant between-group differences were seen in the best overall response rate, progression-free survival, or overall survival. Our data show that outcomes of patients with GI tract involvement before CAR T cell therapy are similar to those without GI involvement, and that durable remissions can be observed. However, patients with preexisting GI tract involvement are at risk of perforation from disease progression before and after CAR T cell infusion.

• Authors: Albert Cortes-Bullich, Ariel Perez, Christina Bachmeier, Rahul Mhaskar, Julio C Chavez, Bijal Shah, Taiga Nishihori, Farhad Khimani, Aleksandr Lazaryan, Marco L Davila, Frederick L Locke, Michael D Jain
• Journal: Transplantation and cellular therapy (Transplant Cell Ther) Vol. 27 Issue 9 Pg. 768.e1-768.e6 (09 2021) ISSN: 2666-6367 [Electronic] United States
• PMID: 34077811 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Chemical References

• Receptors, Chimeric Antigen

Topics

• Cell- and Tissue-Based Therapy
• Gastrointestinal Tract
• Humans
• Immunotherapy, Adoptive
• Lymphoma, Large B-Cell, Diffuse (therapy)
• Receptors, Chimeric Antigen
• Retrospective Studies