Abstract A125: Managing Immune-Related Adverse Events (irAEs) During Tumor Infiltrating Lymphocyte (TIL) Therapy: Insights from a Case of Refractory Immune Checkpoint Inhibitor (ICI)-Induced Gastritis
Authors: Darwin Alicia H , Kim Karen C , Kirane Amanda R , Funchain Pauline , Warner Allison Betof 
Published: February 2025

Background:Immunotherapy continues to revolutionize melanoma treatment. The major side effects of ICIs are irAEs, where off-target immune activation damages healthy tissues. Management of irAEs is immunosuppression. The first TIL therapy, lifileucel, recently gained FDA approval for patients with melanoma refractory to ICI. Adverse events from lifileucel are largely driven by lymphodepletion and IL-2. However, patients may have pre-existing irAEs that could flare in the TIL-induced hyperinflammatory state. Steroids are avoided in the peri-TIL setting given their suppressive impact on effector T-cells and concern for impaired anti-tumor efficacy. Case:We present a 78-year-old female with metastatic acral lentiginous melanoma. She was initially diagnosed with stage IIIC BRAF wild type melanoma and underwent resection and 3 cycles of adjuvant pembrolizumab until disease progression. She then received 2 cycles of ipilimumab/nivolumab then 4 cycles on a clinical trial of GIM-122, a dual functioning monoclonal antibody acting on the PD-1 pathway. She tolerated treatment with mild side effects but had refractory disease. Within a month post treatment discontinuation, she developed nausea and weight loss refractory to antiemetics. CT abdomen and MRI brain were nonrevealing. EGD showed erythema in the gastric antrum and pyloric ulcer; pathology showed increased crypt apoptosis, increased intraepithelial lymphocytes, and villous blunting consistent with ICI gastritis and duodenitis. She received 1 dose of infliximab with symptom resolution then proceeded with lifileucel. She received 3/6 doses of IL-2 until discontinuation for tachyarrhythmia and hallucinations, which resolved with discontinuation. Her GI symptoms flared post-lifileucel, so she started oral budesonide and vedolizumab for GI-targeted immunosuppression to minimize effects on systemic immunity. Repeat biopsies showed minimal crypt apoptosis in the duodenum and chronic active gastritis. Her 6-week post TIL scans showed mixed response. At 8 weeks post-TIL she received a dose of systemic steroids for refractory symptoms. Scans 10 weeks post-TIL showed progressive disease, and her GI symptoms were palliated with systemic steroids. Discussion:This case describes a patient with history of ICI exposure and irAE who proceeded with TIL therapy after which her irAE symptoms flared. Given desire to preserve the TILs’ anti-tumor efficacy, non-steroid agents were initially pursued. Steroids suppress the innate and adaptive immune system by decreasing leukocyte adhesion, promoting an immunosuppressive cytokine milieu, and downregulating effector T-cells with upregulation of regulatory T-cells. Preclinical evidence suggests steroids impair anti-tumor efficacy of TILs whereas anti-TNF agents have less impact. Patients may enter TIL therapy with an irAE history or develop them during treatment, particularly given ongoing studies combining ICI and TILs. It is not clear how to best manage irAEs peri-TIL therapy. More research is needed to understand how immunosuppressants impact the efficacy of TILs.

Citation Format: Alicia H Darwin, Karen C Kim, Amanda R Kirane, Pauline Funchain, Allison Betof Warner. Managing Immune-Related Adverse Events (irAEs) During Tumor Infiltrating Lymphocyte (TIL) Therapy: Insights from a Case of Refractory Immune Checkpoint Inhibitor (ICI)-Induced Gastritis [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A125.