Study Protocol to Characterize Symptom Experience During Immune Checkpoint Inhibitor Therapy for Cutaneous Melanoma

Treatment of patients with stages IIB to IV cutaneous melanoma with immune checkpoint inhibitors (ICIs) have resulted in dramatic improvements in mortality rates. With this rapid shift in treatment, significant gaps in knowledge exist regarding the effect of ICIs on patients' symptom experiences. An in-depth characterization of inter-individual differences in symptom experiences and the identification of risk factors associated with a worse symptom experience will fill this gap and assist with early detection of ICI toxicity, guide symptom management, inform treatment decision-making, and refine ICI-symptom instrument development.

Across four ICI cycles for patients with stage IIB to IV cutaneous melanoma, study objectives are to describe the occurrence, severity, and distress of 53 symptoms; identify symptom clusters based on symptom dimensions (i.e., occurrence, severity, distress); evaluate the stability and consistency of symptom clusters across symptom dimensions and time; identify subgroups of patients with distinct symptom profiles; and evaluate for differences among the symptom profiles in demographic and clinical characteristics and levels of cancer-related stress, financial toxicity, and quality of life (QOL).

This longitudinal, descriptive study is recruiting 300 adults with stage IIB to IV cutaneous melanoma who will start an ICI regimen and following them for four cycles. Participants complete demographic, stress, financial toxicity, and QOL questionnaires prior to their first and fourth ICI cycles. Prior to each cycle, participants report the occurrence, severity, and distress of 53 symptoms using a modified version of the Memorial Symptom Assessment Scale. Symptom clusters will be identified using exploratory factor analysis. Subgroups of participants with distinct symptom profiles will be identified across the ICI cycles using latent class and latent profile analysis. Differences among the latent classes will be evaluated using parametric and nonparametric tests.

Participant recruitment began in October 2025 and will be completed in June 2027.

This study will fill important knowledge gaps about inter-individual differences in risk factors for a worse symptom experience in adults with cutaneous melanoma receiving ICIs. This knowledge is critical to inform clinical assessment and monitoring of high-risk patients and to inform future biomarker research and intervention development.