Mohammad Alomari, MD1, Suleiman Al Ashi, MD1, Laith Al Momani, MD2, Fredy Nehme, MD3, Muhammad Talal Sarmini, MD1, Mark Young, MD2, Pauline Funchain, MD1, Carlos Romero-Marrero, MD, MSc4
1Cleveland Clinic Foundation, Cleveland, OH; 2East Tennessee State University, Johnson City, TN; 3University of Missouri, Kansas City, MO; 4Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH
Introduction: Immune checkpoint inhibitors (iCPI) have recently gained an essential role in treating cancer at advanced stages. However, it has been associated with the development of gastrointestinal immune-related adverse events (GI-IrAEs). We aimed in our study to assess the incidence and nature of GI-IrAEs as well as to investigate the effects of developing GI-IrAEs on cancer response to iCPI and overall survival.
Methods: We retrospectively identified adult patients diagnosed with end-stage malignancy who were treated with any iCPI at our tertiary center between 8/2014 and 8/2017. Charts were reviewed for baseline characteristics, immunotherapy regimens, response to treatment, development of GI-IrAEs, and patient’s overall 1-year survival. Patients in whom the etiology of GI-IrAEs was unclear were excluded. The overall 1-year survival was calculated from the date of treatment initiation and estimated by the Kaplan-Meier method.
Results: We included 492 patients with end-stage cancer receiving iCPI. The majority of patients were white 451(92%) with a median age of 64.5 years. (Table 1) GI-IrAEs were in the form of autoimmune hepatitis 18(48.5%), autoimmune colitis 16(43.5%), autoimmune pancreatitis 4 (11%), and a combination of autoimmune colitis and hepatitis in 1 patient. (Figure 1) Brain cancer was associated with the highest risk of GI-IrAEs 16 (44.4%) followed by renal cell carcinoma 7 (19.4%). Nivulomab was associated with the highest risk for GI-IrAEs (55.6%) followed by Pembrulizumab 14 (38.9%). Forty-one percent of Patients who developed GI-IrAEs had an adequate cancer response to immunotherapy compared to 25.7% in patients without GI-IrAEs (P-value= 0.022). Eighty- three percent of patients whose cancer responded to iCPI survived at 1 year compared to 36 % among non-responders (P < 0.0001). Seventy-eight percent of patients who developed GI-IrAEs survived at 1 year compared to 53% in patients without GI-IrAEs (P < 0.005).
Discussion: The incidence of gastrointestinal toxicity associated with iCPI is second only in frequency to dermatological toxicity. In our study, among the white population with end-stage cancer receiving iCPI, autoimmune hepatitis, colitis, and pancreatitis were fairly common and associated with better cancer response to immunotherapy and overall survival at 1 year. GI-IrAEs might be an indicator of immune system activation, thus may be a reason to continue, rather than discontinue, immunotherapy agents as tolerated.
Citation: Mohammad Alomari, MD; Suleiman Al Ashi, MD; Laith Al Momani, MD; Fredy Nehme, MD; Muhammad Talal Sarmini, MD; Mark Young, MD; Pauline Funchain, MD; Carlos Romero-Marrero, MD, MSc. P0606 - IMMUNE CHECKPOINT INHIBITORS-RELATED GASTROINTESTINAL TOXICITY IS ASSOCIATED WITH BETTER OVERALL SURVIVAL AND TREATMENT RESPONSE IN CANCER PATIENTS. Program No. P0606. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.