First-Line Nivolumab Plus Ipilimumab in Inoperable Epithelioid Malignant Pleural Mesothelioma: Real-World Experience From an Indian Tertiary Care Center.

Background Malignant pleural mesothelioma (MPM) is a highly aggressive, rare malignancy with poor prognosis. Standard frontline treatments have traditionally relied on platinum-based chemotherapy doublets, which offer limited long-term survival benefit. This study evaluates the efficacy, clinical-demographic profile, and safety of first-line dual checkpoint inhibition using nivolumab and ipilimumab in patients with inoperable MPM within an Indian tertiary care setting. Materials and methods A retrospective study was conducted from January 2021 to August 2023 at a single tertiary care center in India. Fifteen patients aged ≥ 18 years with histologically confirmed, previously untreated, metastatic/inoperable epithelioid MPM and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 were included. Patients received nivolumab (240 mg intravenously every two weeks) combined with ipilimumab (1 mg/kg intravenously every six weeks) until disease progression or unacceptable toxicity. Response assessments were performed using positron emission tomography (PET) scans at three months using modified RECIST criteria. The primary objective of this study was to evaluate the real-world overall survival (OS), including median OS and one-year OS and safety profile. Secondary objectives included the assessment of objective response rate (ORR) at first reassessment using modified RECIST criteria and the characterization of the clinical-demographic landscape of this population and toxicity profile. Results The cohort consisted of 15 patients (median age: 65 years, range: 40-76), comprising eight males (54%) and seven females (46%). The median number of administered treatment cycles was seven for nivolumab (range: 2-26) and three for ipilimumab (range: 1-10). At the three-month evaluation, nine patients (60%) achieved a partial response, maintaining a stable response through the 12-month follow-up. Six patients (40%) experienced disease progression after the initial assessment, experiencing an OS of less than nine months. At the 12-month endpoint, the one-year OS rate was 60%, with nine patients alive and continuing immunotherapy. Treatment-related adverse events (TRAEs) occurred in 12 patients (80%), with Grade 3 or 4 TRAEs reported in four patients (26%). The most common all-grade TRAEs were diarrhea (26%), hypothyroidism/thyroiditis (20%), and rash (13%). Grade 3/4 toxicities included hepatitis (6%) and severe diarrhea (13%). Conclusion First-line treatment with combined nivolumab and ipilimumab demonstrates promising clinical efficacy, durable responses, and a manageable safety profile in Indian patients presenting with inoperable epithelioid MPM. These real-world outcomes align closely with global clinical trial benchmarks, supporting a chemotherapy-free dual-immunotherapy strategy. Larger prospective randomized trials are needed to validate these findings within the regional population.