Vitamin D intake is associated with decreased risk of immune checkpoint inhibitor-induced colitis.

BACKGROUND: There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis. METHODS: We performed a retrospective analysis of melanoma patients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination ICIs between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariable logistic regression analyses. External confirmation was performed on an independent cohort from Massachusetts General Hospital. RESULTS: The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). Vitamin D use was recorded in 66/213 patients (31%) before starting ICIs. In multivariable regression analysis, vitamin D use conferred significantly reduced odds of developing ICI colitis (OR 0.35, 95% CI 0.1-0.9). These results were also demonstrated in the confirmatory cohort (OR 0.46, 95% CI 0.2-0.9) of 169 patients of whom 49 developed ICI colitis (29%). Pre-treatment neutrophil-to-lymphocyte ratio (NLR) ≥5 predicted reduced odds of colitis (OR 0.34, 95% CI 0.1-0.9) only in the discovery cohort. CONCLUSIONS: This is the first study to report that among patients treated with ICIs, vitamin D intake is associated with reduced risk for ICI colitis. This finding is consistent with prior reports of prophylactic use of vitamin D in ulcerative colitis and graft-versus-host-disease. This observation should be validated prospectively in future studies.

Organ Preservation in Colon Cancer: An Illustrative Case Report.

The organ preservation strategy in non-metastatic rectal cancer is a rapidly evolving, novel treatment paradigm that is offered outside of a clinical trial in many advanced cancer centers. However, for non-metastatic colon cancer, upfront surgery followed by adjuvant chemotherapy in patients deemed at risk of cancer recurrence is the current standard of care. A significant proportion of patients with non-metastatic colon cancer harbor a deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) signature in tumors, which predicts a deep and durable response to immune checkpoint inhibitors (ICI) in a large proportion of such patients. This opens an opportunity for organ preservation in colon cancer in select circumstances. Herein, we describe a patient with locally advanced dMMR/MSI-H colon cancer who could not undergo standard colon surgery but achieved complete remission following treatment with ICI.

Exclusion of patients living with HIV from cancer immune checkpoint inhibitor trials.

Emerging retrospective and prospective studies indicate that immune checkpoint inhibitors (ICIs) can be safe and effective cancer treatments among people living with human immunodeficiency virus (PLWH), however this high-cancer-risk population has often been excluded from groundbreaking cancer ICI trials. Our study aimed to characterize the current rate of exclusion and conditional inclusion of PLWH in cancer ICI trials by tumor type, trial phase, and year. ClinicalTrials.gov cancer ICI trials with planned starts between 1/1/2019 and 10/20/2020 were identified. Based on trial eligibility criteria, trials were categorized as "excluded" if PLWH could not enroll, "conditionally included" if only PLWH with adequate immune function were allowed, or "included/not specified" if HIV was not mentioned in the eligibility criteria. Trials from 2014 were separately collected for comparison over time. The number of trials excluding PLWH were compared to the included/not specified group using Fisher's exact test. Of 809 trials analyzed from 2019 to 2020, 74.4% excluded, 6.9% conditionally included, and 18.7% included/did not specify PLWH. Early phase trials excluded PLWH more frequently than late phase trials. The 2019-2020 trial cohort showed no significant change in exclusion of PLWH compared to 2014. Despite increasing evidence for safe and effective ICI use for PLWH, most cancer ICI trials exclude PLWH and few studies permit PLWH to participate, even if HIV is well-controlled.