Immune checkpoint inhibitors (ICIs) in deficient mismatch repair (dMMR)/microsatellite instability (MSI) non-colorectal cancers: Real world Indian data and the use of alternative dosing.

Abstract

347 Background: Immune checkpoint inhibitors, predominantly pembrolizumab and dostarlimab, have been approved in deficient mismatch repair (dMMR)/ microsatellite instability (MSI) non-colorectal cancers. There is also an emerging data to suggest significant clinical activity for low-dose ICIs (LD-ICIs) in these cancers. Methods: A multi-institutional retrospective analysis in Indian patients with dMMR/MSI-H advanced/metastatic non-colorectal carcinomas treated with ICIs (irrespective of dose or schedule) between 2017 and 2024 was conducted. The primary objective of the study was to evaluate 12-month Overall survival (OS) for the whole cohort as well as LD-ICI and standard dose ICI (SD-ICI) cohorts, while other secondary objectives included assessment of overall response rates (ORR) (assessed by RECIST v1.1 as per local radiological reporting), 12-month progression free survival (PFS) and incidence of immune related adverse events (IRAEs). Results: A total of 51 patients were available for analysis. The most common tumour types were gastrointestinal (64%, commonly gastric cancer, oesophageal cancer and cholangiocarcinoma) and endometrial cancers (23%). Eighty-four percent of patients received ICI monotherapy, while the remaining 16% received varying combinations of ICIs with chemotherapy and tyrosine kinase inhibitors. Nivolumab was used in 24 patients (47%) while pembrolizumab was used in 17 patients (33%). With a median follow-up of 14 months, 12-month OS was 72% and 12-month PFS was 62% in the entire cohort. The corresponding 12-months OS and 12-month PFS for those receiving SD-ICIs (n=29) was 69% and 62%, while it was 72% and 64%, respectively for the LD-ICIs cohort (n=22). The ORR was 61%, with 10 patients (20%) achieving complete response (CR) and 21 (41%) achieving partial response (PR). The most common IRAEs (all grades) were fatigue (62%), thyroid disturbances (37%), and pruritus (23%). Conclusions: The current study from India highlights the importance of treating non-colorectal dMMR/MSI-H cancers with ICIs and shows outcomes commensurate with published trial data. Within the confines of a small retrospective study with a short follow-up, low dose ICIs should be explored in these patients in scenarios where standard dosing schedules are not feasible due to logistic reasons. Key Words – Low dose immunotherapy; non-colorectal dMMR/MSI-H cancers; Overall survival.