Assessing benefits and harms of cannabis use in patients treated with immunotherapy for cancer: a prospective cohort study

Project Abstract Up to 40% of patients report using cannabis for symptom management during and after cancer treatments despite gaps in our understanding of its longitudinal therapeutic uses and harms. Simultaneously, immuno- oncology is a rapidly advancing field of cancer treatment. Nearly 44% of cancer patients across 20 tumor types

receive treatments with immunotherapy, notably Immune Checkpoint Inhibitors (ICIs), which can lead to persistent changes in the immune system for months or even years. Given cannabis also has immunomodulatory effects, there is a critical need to generate long-term data on the impact of cannabis use on longitudinal benefits

and harms, immune function, and disease progression in cancer patients treated with ICIs. This proposal builds upon our existing program of research. Our team has conducted 4 NCI-funded projects regarding cannabis use in cancer patients, including 3 large cross-sectional surveys of cannabis use among patients treated at 3 NCI

designated cancer centers. Across sites, 26% (n=831 of 3,169) of cancer patients reported using cannabis during treatment. However, the rate was considerably higher among patients treated with immunotherapy (32%). The overarching goal of this study is to advance the science regarding the longitudinal benefits and harms of

cannabis use among those treated with ICIs for cancer. We propose a multi-site, 12-month prospective cohort study (N=450; 150 per site) with cancer patients treated with ICI (within 3 months): 225 cannabis users (regular weekly use in the prior month) and 225 cannabis non-users (no use in the past 6 months). Cannabis use,

benefits, and harms will be assessed via ecological momentary assessment (collected 7 days/time point; 49 days total), patient reported outcomes will be assessed via online/phone surveys, and routine clinical data will be extracted from electronic medical records. Among a subset of 60 patients who have not yet started ICI

treatment (30 cannabis users; 30 non-users), we will examine immunological markers (e.g., TNF-α, IL-6, CRP) at baseline (prior to starting ICI), 2, 6, & 12 months. The Specific Aims are to: 1) assess benefits (pain severity & interference, sleep disturbance, anxiety, quality of life) and harms (difficulty concentrating, impaired memory,

dizziness, fatigue) of cannabis use over time; 2) test whether cannabis use over time moderates the associations between neighborhood disadvantage (Area Deprivation Index) and benefits and harms in Aim 1; & 3) among a subset of 60 patients with non-skin solid malignancies who have not yet started ICI, explore the association of

cannabis use with disease progression and immunological markers. This timely and comprehensive study, in response to RFA-CA-22-052, will fill critical gaps in knowledge about longitudinal benefits and harms of cannabis use in persons treated with ICIs. The strong multidisciplinary team brings the requisite expertise in cancer

symptom management, medical cannabis, health equity, oncology, immunology, and substance misuse. In collaboration with other funded U01s and U24, this research will have a sustained impact on the science of cancer symptom management and ultimately improve patient care and safety.