THU299 Safety Of Immune Checkpoint Inhibitor Cancer Therapy In Patients With Pre-existing Type 1 Diabetes Mellitus: A Multi-Center Cohort Study
Authors: Hilder Robin , Karen Tsai , Isaacs Dayna , Drakaki Alexandra , Lechner Melissa G 
Published: October 2023

Disclosure: R. Hilder: None. T. Karen: None. D. Isaacs: None. A. Drakaki: None. M.G. Lechner: None.

Introduction: Immune checkpoint inhibitors have revolutionized cancer therapy, producing dramatic tumor shrinkage and durable responses in many advanced malignancies. A limitation of their use is the development of unwanted autoimmunity in healthy tissues, known as Immune Related Adverse Effects (IRAEs), that occur in up to 60% of patients and often affect endocrine organs. For this reason, patients with pre-existing autoimmune diseases, including type 1 diabetes mellitus, have systemically been excluded from clinical trials of ICI therapy. This exclusion has translated to current clinical practice and therefore little is known about the safety and efficacy of ICI in this population. Here we report, for the first time, outcomes in ICI-treated patients with pre-existing T1DM. Methods: This retrospective cohort study included adult patients who received an-FDA approved ICI therapy for solid malignancies from 2015-2021 at two academic medical centers (UCLA Health and City of Hope) and had a diagnosis of T1DM prior to starting ICI. ICD-10 codes E10.9 and E10.65 identified 58 patients with T1DM, screened by manual chart review for inclusion. Patients with prior ICI therapy, bone marrow transplant, or pregnancy were excluded. We collected data on demographic, cancer diagnosis and treatment (stage, ICI therapy, response), Grade 3 or 4 IRAEs [classified by the NIH Common Terminology Criteria for Adverse Events (CTCAE) V5] and diabetes management during ICI therapy, including the incidence of significant hyperglycemia, diabetic ketoacidosis (DKA), and the use of technology. Results: Of 7545 ICI treated cancer patients, we identified five with a pre-existing diagnosis of T1DM. Three were female and mean age was 58 years (range 37-79). All patients were diagnosed with metastatic cancer (cervical, lung and breast) and were treated with anti-PD1/PDL1 monotherapy: Nivolumab, Durvalumab, or Pembrolizumab. Two patients had Grade 3 hepatitis, one of which with concurrent myositis requiring prolonged corticosteroids and IVIG. Both patients recovered with cessation of ICI. Regarding other endocrine IRAEs, one patient had pre-existing hypothyroidism and another developed ICI-thyroiditis during ICI therapy; both were treated with thyroid hormone replacement. Four (80%) utilized insulin pump therapy while on immunotherapy. No patients were hospitalized for DKA or complications of hyperglycemia during ICI therapy. Regarding tumor response to ICI, two patients had complete response, two with partial response, and one was deceased shortly after starting therapy. Discussion: Based on this data, ICI monotherapy can successfully be used in patients with pre-existing T1DM, but patients should be counseled on the risk of IRAEs; in particular hepatitis. Larger, prospective studies of these potentially life-saving ICI therapies that include patients with pre-existing autoimmunity are warranted.

Presentation: Thursday, June 15, 2023