Comparison of adverse effect profile of PD-1 and CTLA-4 inhibitors and its variation with race and BMI.

Abstract

e14620 Background: Immune checkpoint inhibitors (ICIs) are the new standard of care for treating various cancers, either alone or in combination. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors and programmed death receptor-1 (PD-1) monoclonal antibodies are the two most common types of ICIs, associated with multiple immune-related adverse events (irAEs). However, there are limited studies assessing the side effects of ICIs and their relationship with race and body mass index (BMI). We aim to compare the adverse effect profiles of PD-1 and CTLA-4 inhibitors and their variation with race and BMI. Methods: A retrospective analysis was conducted on 244 patients who experienced irAEs after receiving ICIs at three centers in New Jersey. Of the population, 57% were female, 81% White, 16% Hispanic, and 3% African American. Patients received pembrolizumab (73%), nivolumab (19%), or a combination of ipilimumab and nivolumab (8%). IrAEs were defined and graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5. Depending on BMI, patients were categorized as “underweight” (<18.5 kg/m²), “normal weight” (18.5–24.9 kg/m²), “overweight” (≥25 kg/m²), or “obese” (≥30 kg/m²) as per World Health Organization. Results: Patients on pembrolizumab and nivolumab had similar rates of colitis (17% vs 15%) and hepatitis (34% vs 37%). The ipilimumab/nivolumab combination had lower incidence of colitis (6%) but higher rates of hepatitis (47%). Pembrolizumab recipients had higher colitis rates in normal/low-weight patients (34%) compared to overweight/obese (20%), while the reverse trend was seen with nivolumab alone (19% vs 21%) and the combination (0% vs 20%). Higher BMI pembrolizumab recipients showed increased hepatitis rates (38% vs 29%). Overweight/obese patients had more dermatitis and thyroiditis across ICIs (28% vs 14%; 30% vs 35% for pembrolizumab, 29% vs 14%; 54% vs 28% for nivolumab, and 37% vs 11%; 37% vs 11% for the combination) respectively. Lower-BMI patients had more anemia than obese patients (54% vs 39%; 33% vs 16%; 44% vs 12%) and more thrombocytopenia and neutropenia with pembrolizumab (21% vs 12%; 35% vs 27%) but less with nivolumab (14% vs 17%; 23% vs 29%). Higher rates of colitis (27% vs 13%), dermatitis (23% vs 6%), anemia (44% vs 22%), and neutropenia (28% vs 19%) were seen in Whites compared to Hispanics, while hepatitis, thrombocytopenia, and pneumonitis rates were similar. Thyroiditis was more frequent in Hispanics as compared to whites (45% vs 35%). African Americans had high rates of neutropenia (80%) and thyroiditis/dermatitis (40%). Conclusions: Overall, there was a higher incidence of IrAEs in patients of higher BMI and Whites but the pattern was not very consistent with hematological adverse effects.