Immune checkpoint blockade therapy of mesothelioma: a clinical and radiological challenge

Our plain-English summary of Immune checkpoint blockade therapy of mesothelioma: a clinical and radiological challenge, by L. Calabrò, A. Morra, R. Cornelissen, et al (Cancer Immunology, Immunotherapy, 2018).

The study

• Authors: L. Calabrò, A. Morra, R. Cornelissen, J. Aerts, M. Maio
• Journal: Cancer Immunology, Immunotherapy
• Published: 2018;67(8):1317-1324
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Treatment of malignant pleural mesothelioma (MPM) represents a highly unmet medical need. Here, we discuss the results and therapeutic potential of first- and second-generation immunomodulatory antibodies targeting distinct immune checkpoints for the treatment of MPM, as well as their prospective therapeutic role in combination strategies. We also discuss the role of appropriate radiological criteria of response for MPM and the potential need of ad hoc criteria of disease evaluation in MPM patients undergoing treatment with immunotherapeutic agents.

In plain English

This article was a focused review, not a new study. The authors discussed published and ongoing trials of immune checkpoint antibodies (tremelimumab, ipilimumab, pembrolizumab, nivolumab, durvalumab, avelumab) for malignant pleural mesothelioma, and in some trials peritoneal mesothelioma. They also discussed the difficulty of measuring tumour response on scans. Among the trials described, the DETERMINE trial of 564 patients found that tremelimumab did not improve overall survival compared with placebo. In the NIBIT-MESO-1 trial, 40 patients received tremelimumab with durvalumab. In that trial, 27.5% had an immune-related objective response, 65% had disease control, and median overall survival was 16.6 months. The authors cautioned that early results with PD-1 and PD-L1 antibodies were preliminary and used different scan criteria. They also described three men with malignant pleural mesothelioma treated in these trials whose tumours responded in different patterns. In one of them, the disease first appeared to progress at week 6 and showed a partial response at week 80. The authors proposed adding immune-related criteria to modified RECIST, called "ir-m-RECIST". They concluded that these antibodies were beginning to show clinical potential.

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: Focused research review of clinical trials of immune checkpoint antibodies in mesothelioma and of radiological response criteria, illustrated with three clinical case descriptions
• Who was studied: Patients with malignant pleural mesothelioma (and, in some trials reviewed, peritoneal mesothelioma) enrolled in the trials discussed; plus three individual patients with malignant pleural mesothelioma described as cases (men aged 67, 64 and 59)
• Exposure: Treatment with immune checkpoint antibodies: anti-CTLA-4 (tremelimumab, ipilimumab), anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 (durvalumab, avelumab), alone or in combination. This is a treatment review; asbestos exposure was not studied.
• Main results:
  • As reviewed by the authors: in the DETERMINE trial of 564 malignant pleural or peritoneal mesothelioma patients, tremelimumab did not improve overall survival (the primary endpoint) compared with placebo. Grade 3 or higher treatment-related toxicity occurred in 29% of tremelimumab-treated patients.
  • As reviewed: in the MESOT-TREM-2012 trial of 29 patients given an intensified tremelimumab schedule, there were 4 immune-related partial responses (14%) and an immune-related disease control rate of 52%. Median overall survival was 11.3 months (95% CI 3.4–19.2).
  • As reviewed: in the NIVO-MES phase II study of nivolumab in pre-treated malignant pleural mesothelioma patients, the objective response rate was 24% and the disease control rate was 50%.
  • As reviewed: in the NIBIT-MESO-1 trial of 40 mesothelioma patients given tremelimumab plus durvalumab, the immune-related objective response rate was 27.5% and the immune-related disease control rate was 65%. Median overall survival was 16.6 months. As of April 2017, 17% had grade 3–4 treatment-related toxicity.
  • As reviewed: in the MAPS-2 trial, the disease control rate at 12 weeks was 44% with nivolumab alone and 50% with nivolumab plus ipilimumab.
  • Case 3: a 59-year-old man treated with tremelimumab in the DETERMINE study. His scan showed progression at week 6, stable disease at week 12 and partial response at week 80. New peritoneal lesions appeared at week 96. The authors described this as a delayed tumour response.
  • The authors proposed adding immune-related criteria to modified RECIST, creating 'ir-m-RECIST' for malignant pleural mesothelioma. These criteria were first used in the NIBIT-MESO-1 study.
• The authors' conclusion: The authors concluded that immune checkpoint blocking antibodies were beginning to show clinical potential in malignant pleural mesothelioma and that further studies would explore their role.
• Limitations the authors state:
  • The authors cautioned that results from early-phase PD-1/PD-L1 studies were still preliminary, used different radiological evaluation criteria, and came mostly from studies that were still ongoing.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma.

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• Moving Immune Checkpoint Blockade in Thoracic Tumors beyond NSCLC — F. Facchinetti, A. Marabelle, et al. (2016)
• Immune checkpoint blockade in malignant mesothelioma — L. Calabrò, M. Maio (2015)
• Immune checkpoint inhibitors in malignant pleural mesothelioma: promises and challenges — G.L. Ceresoli, M. Bonomi, et al. (2016)
• Combination immune checkpoint blockade as an effective therapy for mesothelioma — V.S. Fear, C. Tilsed, et al. (2018)
• Success of Checkpoint Blockade Paves the Way for Novel Immune Therapy in Malignant Pleural Mesothelioma — L. Rondon, R. Fu, et al. (2023)

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