CASE REPORT article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1671503
This article is part of the Research TopicThe Role of Immunotherapy in Cancer Therapy and Its ChallengesView all 6 articles
IL-6 Suppression: a Potential Strategy for Mitigating Severe Immune-Related Adverse Events in Nivolumab and Ipilimumab Therapy for Malignant Pleural Mesothelioma
Provisionally accepted
- JCHO Tokyo Shinjuku Medical Centor, Tokyo, Japan
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Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer with a poor prognosis, often presenting challenges in treatment. The CheckMate-743 trial demonstrated significant improvements in overall survival with the combination therapy of nivolumab and ipilimumab in advanced MPM. However, the management of immune-related adverse events (irAEs) remains a critical concern. Case presentation: We present a 74-year-old male with a history of polymyalgia rheumatica (PMR), diagnosed two years prior. His PMR was initially treated with corticosteroids, but tapering the dose was difficult. Therefore, tocilizumab was initiated one year before the current presentation, leading to a stable remission. One month before starting cancer therapy, tocilizumab was discontinued while the patient's PMR remained well-controlled. He then developed multiple serious irAEs following the first cycle of nivolumab and ipilimumab for advanced MPM. These included cytokine release syndrome (CRS), immune-related aseptic meningitis, and liver dysfunction. All irAEs were successfully managed with corticosteroids, and the patient's tumor progression remained under control. Conclusion: This case suggests that residual IL-6 suppression from prior tocilizumab therapy may attenuate the severity of subsequent irAEs, permitting effective management without compromising anti-tumor efficacy. IL-6 modulation could be a promising strategy to improve the therapeutic index of dual checkpoint inhibition in MPM.
Keywords: malignant pleural mesothelioma1, Immune checkpoint inhibitor 2, Nivolumab3, Ipilimumab 4, ipilimumab5, Immune-Related Adverse Events (irAEs)6, IL-67, Tocilizumab8
Received: 23 Jul 2025; Accepted: 16 Oct 2025.
Copyright: © 2025 Yanagisawa, Fukaya, Noda, Kojima and Shimizu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Asako Yanagisawa, asa.yan44@gmail.com
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