Correlation between immune-related adverse events and therapeutic effects of nivolumab in patients with malignant pleural mesothelioma

Our plain-English summary of Correlation between immune-related adverse events and therapeutic effects of nivolumab in patients with malignant pleural mesothelioma, by H. Yoneda, H. Nokihara, A. Mitsuhashi, et al (BMC Pulmonary Medicine, 2021).

The study

• Authors: H. Yoneda, H. Nokihara, A. Mitsuhashi, R. Ozaki, Y. Yabuki, H. Ogino, K. Otsuka, Y. Nishioka
• Journal: BMC Pulmonary Medicine
• Published: 2021;21(1):373
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Nivolumab is used for the treatment of malignant pleural mesothelioma (MPM). However, immune-related adverse events (irAEs) occur in patients treated with nivolumab. Several studies have reported the correlation between irAEs and therapeutic effects of immune checkpoint inhibitor, but none have reported the correlation in MPM. Here we report a retrospective study which shows the correlation between irAEs and therapeutic effects of nivolumab in patients with MPM.

Methods: This study included patients treated with nivolumab at Tokushima University Hospital from February 2009 to September 2021. We retrospectively reviewed the medical records to evaluate the several clinical factors, such as the presence or absence of irAEs, their severities, progression-free survival (PFS), overall survival (OS) or objective response to the treatment.

Results: Eleven patients received treatment with nivolumab. Objective response rate was 18.2% and the disease control rate was 90.9%. Median PFS was 6.8 months (95% confidence interval, 1.3 to 11.9 months) and median OS was 15.2 months (95% confidence interval, 8.9 to 21.5 months). IrAEs occurred in eight patients (72.7%), and grade ≥ 2 irAEs occurred in six patients (54.5%). PFS and OS were significantly longer in the grade ≥ 2 irAEs group than in grade < 2 irAEs group (median PFS 13.6 vs. 3.8 months, p = 0.0093; median OS not reached vs. 8.6 months, p = 0.0108).

Conclusions: This is the first study to report the correlation between irAEs and therapeutic effects in patients with MPM. Because the presence of irAEs may be associated with a favorable clinical outcome, early detection and appropriate management of irAEs will increase the therapeutic benefits to patients.

© 2021. The Author(s).

In plain English

This retrospective study from Tokushima University Hospital in Japan reviewed the records of 11 patients with malignant pleural mesothelioma, all epithelial type, treated with the immune checkpoint inhibitor nivolumab after platinum and pemetrexed chemotherapy. Six had a history of asbestos inhalation. The authors asked whether immune-related side effects were linked to treatment results. Two patients had a partial response, eight stable disease and one progressive disease. For all 11, median progression-free survival was 6.8 months (95% confidence interval 1.3 to 11.9) and median overall survival 15.2 months (95% confidence interval 8.9 to 21.5). Immune-related side effects occurred in eight patients and reached grade 2 or higher in six. Those six had longer median progression-free survival than the other five (13.6 vs. 3.8 months, p = 0.0093). They also had longer overall survival (median not reached vs. 8.6 months, p = 0.0108). Side effects led to stopping nivolumab in three patients, and no deaths from them were seen. The authors concluded that such side effects may be associated with a favorable outcome. They noted the study was small, retrospective and single-center.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective, single-institution review of medical records
• Who was studied: 11 patients with malignant pleural mesothelioma treated with nivolumab. They were drawn from 27 patients diagnosed with the disease at Tokushima University Hospital, Japan, between February 2009 and September 2021. Eight were male and three female, with a median age of 72 (range 56 to 84). All had epithelial-type tumors. Six of the 11 had a history of asbestos inhalation. Ten received nivolumab as second-line treatment and one as third-line treatment.
• Exposure: The study examined the drug nivolumab (an anti-PD-1 antibody), given intravenously at 240 mg every two weeks until disease progression or unacceptable side effects. All patients had first received platinum (cisplatin or carboplatin) plus pemetrexed. Asbestos exposure was recorded only as a patient characteristic (6 of 11 with an inhalation history) and was not analyzed.
• Main results:
  • Best response among the 11 patients: partial response 18.2%, stable disease 72.7%, progressive disease 9.1%, and no complete responses. The objective response rate was 18.2% and the disease control rate 90.9%.
  • For all 11 patients, median progression-free survival was 6.8 months (95% CI 1.3 to 11.9) and median overall survival was 15.2 months (95% CI 8.9 to 21.5).
  • Immune-related adverse events occurred in 8 of 11 patients (72.7%). They were grade 2 or higher in 6 patients (54.5%) and included pneumonitis, hypothyroidism, hypophysitis and skin reactions.
  • Patients with grade 2 or higher immune-related adverse events (n = 6) had longer median progression-free survival than patients with grade below 2 or no such events (n = 5): 13.6 vs. 3.8 months, p = 0.0093. Overall survival was also longer in the first group: median not reached vs. 8.6 months, p = 0.0108.
  • Nivolumab was discontinued and not restarted in three patients: two with pneumonitis and one with hypophysitis. No deaths related to immune-related adverse events were observed.
• The authors' conclusion: The authors concluded that immune-related adverse events may be associated with favorable progression-free and overall survival in malignant pleural mesothelioma treated with nivolumab. They stated that early detection and appropriate management of these events could allow treatment to continue without discontinuation and improve its benefits.
• Limitations the authors state:
  • The sample size was small because the disease is rare and nivolumab was only approved for it in 2018.
  • The study was retrospective and conducted at a single institution, so it may contain selection bias.
  • All tumors were of the epithelial type, so the findings may not apply to other histological types.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Immune-Related Adverse Events, Nivolumab (Opdivo), Pleural Mesothelioma, checkpoint inhibitors, Progression-Free Survival, Overall Survival, confidence interval.

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• Case Report: IL-6 suppression: a potential strategy for mitigating severe immune-related adverse events in nivolumab and ipilimumab therapy for malignant pleural mesothelioma — A. Yanagisawa, T. Fukaya, et al. (2025)
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• Efficacy of Nivolumab in Chemotherapy-Resistant Mesothelioma of the Tunica Vaginalis Testis: A Case Report — H. Koyanagi, T. Kawahara, et al. (2026)

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