Patterns and risk factors of immune-related adverse events in a real-world cohort with lung cancer receiving immunotherapy.

person Xiao Hu Tufts Medical Center (Cancer Center), Boston, MA info_outline Xiao Hu, Anastasia Gurinovich, Stacey Pan, Yana Salei, Jeffrey Lin, Susan K. Parsons

Authors person Xiao Hu Tufts Medical Center (Cancer Center), Boston, MA info_outline Xiao Hu, Anastasia Gurinovich, Stacey Pan, Yana Salei, Jeffrey Lin, Susan K. Parsons Organizations Tufts Medical Center (Cancer Center), Boston, MA, Tufts Medical Center, Boston, MA, Tufts Medical Center/Tufts University School of Medicine, Boston, MA Abstract Disclosures Research Funding Tufts University School of Medicine Background: Immune checkpoint inhibitors (ICIs) have emerged as a core pillar of lung cancer (LC) therapy, but ICIs are commonly associated with a spectrum of immune-related adverse effects (irAEs). The real-world patterns and risk factors of irAEs in LC remain uncertain. Methods: Patients with LC newly started on ICIs between 10/01/2018 and 09/30/2021 were retrospectively collected from the Tufts Medical Center cancer registry and pharmacy records. irAEs occurring within 12 months after initiation of ICIs were identified. Univariable logistic regression was used to assess the risk factors of irAEs. Those with p-value<0.20 were included in multivariable logistic regression analysis (MVA), along with clinically relevant factors. Results: Of 125 LC adult patients (median age: 70 years, 68 males), 104 had non-small cell lung cancer (NSCLC), 123 had advanced stages, and 16 had preexisting autoimmune diseases (ADs). Six patients were treated with dual-agent ICIs. Pembrolizumab was the most often used single agent (67.2%). In total 50 irAEs occurred in 39 patients. The most common irAEs were endocrinopathies (34%), pneumonitis (20%), dermatitis (14%), and gastrointestinal toxicity (14%) with the median onset time of 148, 136, 19, and 68 days, respectively. 70% of irAEs were grade 1 or 2. 44% of irAEs were treated with immunosuppression, 38% were referred to specialist care, and 30% required hospitalizations. 56% of irAEs resolved within 12 months and 67.9 % of those were rechallenged with ICIs. In exploratory univariable analyses among all the patients, age, small cell lung cancer (SCLC), PDL1 positivity (TPS≥1%), concurrent NSAIDs use, and radiation therapy had p< 0.2. In MVA, SCLC remained significantly associated with irAEs (OR=4.14, 95% CI [1.50, 12.09], p=0.007). Among NSCLC subset (N=104), age, PDL1 positivity, concurrent NSAIDs, and acetaminophen use had p<0.2. Age (OR=0.94, 95% CI [0.883, 0.990], p=0.026) and PDL1 positivity (OR=3.17, 95% CI [1.12, 9.87], p=0.036) remained significant in MVA (Table). Conclusions: Our study described the real-world patterns of irAEs in LC patients. SCLC was found to be an independent risk factor of irAEs in our cohort. In NSCLC, younger age and PDL1 positivity were associated with irAEs occurrence. Future studies are required to validate these findings in larger samples. Multivariable regression analyses for the risk factors of IrAEs. All Patients (N=125) NSCLC Patients (N=104) Factors OR p-value OR p-value Age 0.962 0.085 0.937 0.026 Female # 1.411 0.429 1.001 0.999 SCLC 4.141 0.007 PDL1 positivity * 3.172 0.036 Preexisting ADs # 0.952 0.946 0.341 0.366 Concurrent NSAIDs 0.408 0.215 0.207 0.167 Concurrent acetaminophen 0.623 0.506 Concurrent radiation 0.165 0.098 # Sex and ADs history were included in both MVAs as clinically relevant factors. *PDL1 status was not included in the MVA of all patients given only 4 SCLC cases had PDL1 results.