Summary

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• Dostarlimab-gxly (Jemperli) is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), as determined by an FDA-approved test. It can be used in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent. It is also indicated for dMMR recurrent or advanced solid tumors.
• Two systematic reviews/meta-analyses provided insights into the clinical effectiveness, safety profile, and pharmacokinetic characteristics of Jemperli.
• When compared to other immune checkpoint inhibitors such as pembrolizumab, nivolumab, and durvalumab, Jemperli shows a relatively tolerable safety profile. Single-agent immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 exhibit fewer serious treatment-related adverse events than combinations of ICIs with tyrosine kinase inhibitors, which have notably higher toxicity rates.
• The overall response rate for immune checkpoint inhibitors ranged from 26.7% to 58% among MSI-H patients, indicating significant effectiveness in this subgroup. This includes users of Jemperli with dMMR/MSI-H phenotypes, making it a promising option especially when combined with TKIs despite the increased risks of toxicity.
• Patient factors such as body weight, albumin levels, tumor type, sex, and performance status influence the clearance and volume distribution of anti-PD-1 monoclonal antibodies, including dostarlimab-gxly, emphasizing the importance of patient selection and monitoring for effective dosing.
• The responsiveness of MSI-H/dMMR tumors to treatment highlights the value of testing for MSI status in patients diagnosed with endometrial cancer, while personalized approaches could enhance treatment effectiveness based on various patient factors influencing the pharmacokinetics of drugs like Jemperli.