Dataset Information

Characterization of genetics in patients with mucosal melanoma treated with immune checkpoint blockade.

ABSTRACT: Mucosal melanoma is a rare form of melanoma which arises from melanocytes in the mucosal membranes and can be effectively treated with immune checkpoint blockade (ICB). However, response rates in mucosal melanoma are lower than those observed for cutaneous melanomas. Targeted sequencing of up to 447 genes (OncoPanel) was performed on tumors from all mucosal melanoma patients seen at the Dana-Farber Cancer Institute from 2011 until March 2019. We identified a total of 46 patients who received ICB with both tumor-genotype and ICB response data available. Within this cohort of patients, 16 (35%) had durable clinical benefit (DCB) to their first line of ICB. The average mutational burden/megabase was 6.23 and did not correlate with tumor response to ICB. Patients with KIT aberrations had a higher DCB rate compared with patients with wildtype KIT (71 vs. 28%), but this was not found to be statistically significant. For comparison, we analyzed tumor genotypes from an additional 50 mucosal melanoma tumors and 189 cutaneous melanoma tumors. The most frequent mutations in mucosal melanoma were in SF3B1 (27%), KIT (18%), and NF1 (17%), a pattern that is distinct from cutaneous melanomas. In addition, there were genetic differences observed based upon the site of origin of the mucosal melanoma. Our findings explore clinical features of response in patients with mucosal melanoma treated with ICB and demonstrate a low mutational burden that does not correlate with response. In addition, the lack of significant association between the genetic aberrations tested and response to ICB indicates the need for further exploration in this patient population.

SUBMITTER: Buchbinder EI

PROVIDER: S-EPMC8026918 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundReal-world data enables evaluation of immune checkpoint inhibitor (ICI) use in advanced melanoma management. We examined characteristics and outcomes of ICI-treated patients with advanced melanoma and organ dysfunction (baseline and emergent).Materials and methodsThis retrospective observational study used electronic health records derived from a nationwide data set to examine advanced melanoma patients treated with first-line ICIs (2011-2018). Clinical characteristics, real-world time to treatment discontinuation (rwTTD), and overall survival (OS) were analyzed for patients with normal organ function and those with organ dysfunction prior to ICI initiation. Patients with emergent dysfunction in the 90 days following ICI initiation were identified, and potentially associated characteristics were explored.ResultsOf 2,407 patients included, 1,884 and 1,717 had evaluable renal and hepatic laboratory values, respectively. Patients with baseline renal dysfunction (2.4%) were older and more frequently male, and less frequently treated with ICI combinations, than patients with normal renal function. Patients with baseline hepatic dysfunction (2.8%) were similar to patients with normal hepatic function regarding demographics and treatments received. Patients with baseline organ dysfunction displayed shorter rwTTD and OS. Among patients with normal baseline organ function, 4.6% and 7.4% developed renal and hepatic dysfunction within 90 days of ICI initiation, respectively; this was associated with combination ICI treatment.ConclusionPatients with advanced melanoma and baseline organ dysfunction frequently receive ICI treatment but have poorer clinical outcomes than patients with normal organ function. Among patients with normal renal and hepatic function at ICI initiation, emergent organ dysfunction rates in this real-world cohort are similar to those reported in clinical trials.Implications for practiceReal-world data provide an opportunity to understand treatment patterns, toxicity, and clinical outcomes among patients treated outside of clinical trials. This study confirms that patients with advanced melanoma and baseline renal or hepatic dysfunction are being treated with ICI therapy more frequently as monotherapy than in combination therapy. For those real-world patients with normal baseline organ function, emergent renal and hepatic dysfunction are both more common in patients treated with combination versus ICI monotherapy.

Dataset Information

Characterization of genetics in patients with mucosal melanoma treated with immune checkpoint blockade.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets