Immune-related Adverse Events and Symptom Burden in Patients with Melanoma Receiving Adjuvant Immune Checkpoint Inhibitor.

TPS12147 Background: Adjuvant therapy with immune checkpoint inhibitors (ICIs) is approved for melanoma, but immune-related adverse events (irAEs) remain a challenge. Although acute toxicities are well defined, long-term AEs and impact on quality of life (QOL) are undetermined. Available data derived from clinical trials involve highly selected populations and do not reflect real world experience. Additionally, trials measure outcomes only at predetermined endpoints, and symptoms may vary throughout the course of therapy. Moreover, the pathogenesis of irAEs and symptoms remains poorly understood. We hypothesize that AEs and sustained inflammation induced by adjuvant ICIs increase symptom burden and negatively impact function and QOL in a subset of patients (pts), and elevated expression of pro-inflammatory cytokines and T cell signatures during therapy correlate with toxicity and symptom burden. Our preliminary data identified i) interleukin-6/Th-17 pathway as a possible mediator of irAEs, ii) immune reactivity and increases in inflammatory cytokines are associated with symptom burden in cancer survivors, and iii) prioritized 30 genetic markers conferring risk for irAEs in ICI-treated melanoma pts. Methods: This is a prospective longitudinal cohort study to evaluate potential toxicity/symptom burden and immune correlates in melanoma pts receiving adjuvant ICIs (NCT04990726). A total of 240 pts will be enrolled. Eligibility criteria: age ≥18 years (yrs), surgically resected stage II, III, or IV melanoma, initiating adjuvant nivolumab or pembrolizumab, no prior systemic therapy for melanoma, and no prior autoimmune diseases. Patients will be assessed at baseline (before ICI infusion) and every 3 months (mos) up to 2 yrs or until attrition or death. The primary endpoint is the incidence rate of any irAEs at 12 mos. Demographics, personal/family history, comorbidities, tumor history/stage, prior therapies, performance status, concurrent medications, and other factors that play a role in pts perceptions of disease are collected. At each visit, pts undergo a clinical evaluation to assess potential irAEs, new comorbidities, and tumor recurrence. Patient-reported outcomes of fatigue, depression, sleep disturbance, and QOL are collected at each visit to assess changes from baseline up to 2 yrs. In addition to standard methods of data collection at pre-specified times, we leverage mobile technology to capture symptoms and AEs in real time. Longitudinal blood samples will characterize pts immune signatures from baseline up to 2 yrs to evaluate their association with irAEs, symptom burden, and QOL, and to compare the genotype of pts with and without irAEs. To characterize the effect of adjuvant ICI on bone health, eligible pts are evaluated by whole body dual-energy X-ray absorptiometry at baseline and at 12 mos as an exploratory aim. The study is currently active, and 27 pts are enrolled. Clinical trial information: NCT04990726.