First-line nivolumab plus ipilimumab in pleural mesothelioma: Efficacy and safety data from the real-world MesoNet study
- PMID: 40779889
- DOI: 10.1016/j.lungcan.2025.108702
First-line nivolumab plus ipilimumab in pleural mesothelioma: Efficacy and safety data from the real-world MesoNet study
Abstract
Background: Despite the approval of nivolumab/ipilimumab, the prognosis of patients with pleural mesothelioma (PM) remains poor. Although this combination has shown improved survival in the landmark CheckMate (CM)-743 trial, evidence from real-world settings remains limited.
Methods: In this retrospective, multicenter study, the outcome and safety data for 135 consecutive patients with first-line nivolumab/ipilimumab were evaluated among 1,575 adult patients with PM from 12 German cancer centers. Radiologic response and progression were analyzed according to the revised modified RECIST criteria.
Results: The median overall survival (OS) was 13.1 months for the unselected real-world cohort, and 15.5 months for CM-743-eligible patients (16.7 months for the non-epithelioid and 10 months for the epithelioid subtypes). Patients who experienced partial responses to nivolumab/ipilimumab had significantly longer survival than those without (24 months vs. 10.3 months; p = 0.00026). 37 % of patients experienced immune-related adverse events (irAEs), among whom 58 % had grade 3/4 toxicity. IrAEs of any grade were associated with longer survival (17.3 months vs. 11.7 months for patients without irAEs; p = 0.022). Furthermore, grade 1/2 irAEs were associated with even better outcomes when compared to grade 3/4 toxicities (22.7 months vs. 16.7 months median OS) and absence of toxicity (p < 0.0167 for trend).
Conclusions: Overall survival with first-line nivolumab/ipilimumab in the real-world setting is comparable to the CM-743 results among trial-eligible patients, especially with non-epithelioid tumors, but shorter for the unselected cohort. IrAEs, in particular those of low-grade, were associated with better outcomes. In the absence of predictive biomarkers and with few therapeutic options available, both dual checkpoint blockade and platinum-pemetrexed chemotherapy remain viable first-line regimens.
Keywords: Epithelioid; First-line; Immunotherapy; Mesothelioma; Retrospective cohort.
Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RS has received research grant for an investigator initiates trial from Bristol Myers Squibb (BMS) (institutional), compensation for speakers’ bureau and consulting fees from AstraZeneca (AZ), Novartis, SanofiAventis, Johnson&Johnson, MSD and Roche. He holds a leadership role at the pulmo-oncology working group of the German cancer society. ELB has received consulting fees from Janssen, AZ, BMS, Takeda and travel support from Janssen. HGK has received consulting fees from BMS, MSD, AZ, Pfizer, Roche, Johnson&Johnson, Takeda, expert testimony from BMS, MSD, AZ, Pfizer, Roche, Johnson&Johnson, travel support from BMS, MSD, AZ, Pfizer, Roche, Johnson&Johnson, Takeda, and compensation for data safety board from BMS, AZ, MSD, Pfizer, Takeda. DCC has received consulting fee, speakers’ bureau fee, expert testimony, travel support, compensation for data safety board from BMS. FG has received research grants from Amgen, AZ, BI, BMS, Celgene, Daiichi Sankyo (DS), Gilead, GSK, Janssen, Lilly, MSD, Novartis, Pfizer, Regeneron, Roche, Takeda, and has received speakers’ bureau and consulting fee from AZ, BI, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, Abbvie, Siemens, Tesaro/GSK, Amgen, Sanofi, Daiichi-Sankyo, Beigene, Gilead. MR has received consulting and speakers’ bureau fee and travel support from Amgen, AZ, Beigene, BI, BMS, Lilly, Merck, MSD, Mirati, Novartis, GSK, Pfizer, Roche, Regeneron, Sanofi, DS, Janssen, and has been compensated for data safety board from Sanofi, DS. PH has been compensated for data safety board from AZ, MSD, Johnson&Johnson, Lilly, BMS. JK has received travel support from AZ, BMS, and benn compensated for data safety board from Pfizer, AZ, BMS. NF has received research grant to institution from Roche, consulting fee from AbbVie, Amgen, AZ, BeiGene, Berlin Chemie, BI, BMS, Lilly, Merck Sharp&Dohme, Merck, Novartis, Pfizer, Roche, Sanofi, Takeda, travel support from Amgen, AZ, BMS, Janssen, Lilly, Takeda, and holds a leadership role at the German society of pneumology and AIO of German cancer society. CG has received speaker’s fee, consulting fee and travel support from AZ, BMS, Böhringer Ingelheim (BI) and DS. MF has received consulting fee from Roche, BMS, MSD, AZ, and research grant to institution from Roche, BMS, MSD, AZ. MB has received fee for speakers’ bureau from AZ, Roche, and travel support from Merck. MK has received fee for speakers’ bureau and consulting from Janssen, AZ, travel support from Janssen, BMS, BeiGene. PC has received research grant to institution from Roche, Amgen, BI, Takeda, Merck, AZ, Novartis, fee for speakers’ bureau from Roche, Takeda, AZ, Gilead, Merck, Thermo-Fisher, Janssen, Pfizer, Novartis, travel support from AZ, Pfizer, Janssen, Merck, Gilead, DS, Takeda, Novartis, Lilly and consulting fee from Pfizer, Chugai, BI, Takeda, Janssen, Novartis, AZ, MSD, Roche. MT has received research grant to institution from AZ, BMS, Johnson&Johnson, Merck, Pharmamar, Roche, Takeda, fee for consulting and speakers’ bureau from Amgen, AZ, Beigene, BMS, BI, DS, Gilead Sciences, GSK, Johnson&Johnson, Lilly, Merck, MSD, Novartis, Pfizer, Pharmamar, Pierre Fabre, Regeneron, Roche, Sanofi, Takeda and travel support from AZ, BMS, BI, DS, Johnson&Johnson, Lilly, Merck, MSD, Novartis, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Takeda. JL, JR, PChi, TO, HB, LVK, and IC declared no competing interests.
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