Case report: complete response and long-term survival on third-line immunotherapy in patient with pleural mesothelioma

Our plain-English summary of Case report: complete response and long-term survival on third-line immunotherapy in patient with pleural mesothelioma, by Ž. Jurić Čuljak, S. Tomić, K. Šitum, et al (Frontiers in Oncology, 2024).

The study

• Authors: Ž. Jurić Čuljak, S. Tomić, K. Šitum, T. Boraska Jelavić
• Journal: Frontiers in Oncology
• Published: 2024;14:1388829
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Pleural mesothelioma (PM) is a rare neoplasm with median survival time range from 8 to 14 months from diagnosis, and the 5-year survival rate less than 10%, indicating a poor prognosis. The standard treatment for unresectable PM for a long time has been polychemotherapy with pemetrexed and cisplatin for fit patients. Currently, the combination of the anti PD-1 inhibitor nivolumab and the anti-CTLA4 inhibitor ipilimumab has been recognized as the best possible frontline therapy (especially in the sarcomatoid or biphasic type) due to improved outcomes compared to the standard chemotherapy combination. There are still no established predictive biomarkers for any type of systemic therapy in this disease.

Case Presentation: Patient who presented with cough and dyspnea has been diagnosed with advanced epithelioid type PM in May 2016. He was treated with three lines of therapy, including an antiangiogenic agent and immunotherapy with pembrolizumab in the third line. Immunotherapy with the PD-1 inhibitor pembrolizumab achieved a complete and prolonged response that transferred to long- term survival. Seven years from diagnosis, the patient is still alive. Histological findings showed an unusually immune-inflamed tumor microenvironment possibly leading to excellent response on immunotherapy.

Conclusions: The course of the disease in our patient points out that we need better predictive biomarkers to direct the treatment algorithm, as some of the patients, although chemorefractory to the best chemotherapy option, can sustain great benefit of second-line chemotherapy in combination with antiangiogenic agent, and especially immunotherapy, even in late lines of therapy.

Copyright © 2024 Jurić Čuljak, Tomić, Šitum and Boraska Jelavić.

In plain English

This case report from Croatia described one man with pleural mesothelioma. Aged 67, he presented with cough and shortness of breath in April 2016. In May 2016 his right lung and pleura were surgically removed, and tests confirmed diffuse epithelioid pleural mesothelioma that had reached chest lymph nodes. The article does not describe any asbestos exposure for him. His disease grew after two cycles of first-line cisplatin and pemetrexed. Second-line gemcitabine with bevacizumab (15 cycles) partly shrank the tumor before it grew again. He then received 12 cycles of the immunotherapy drug pembrolizumab in 2018, and scans showed a complete response. Treatment stopped because of grade 3 lung inflammation (pneumonitis), from which he recovered. At his last check-up, in August 2023, he remained in complete remission. His tumor contained many immune cells, PD-L1 was found in 2% of tumor cells, and tumor mutation burden was low. The authors concluded that some patients whose disease resists chemotherapy can still benefit greatly from later treatment, and that better ways to predict treatment response are needed.

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: case report (one patient)
• Who was studied: One 67-year-old man with a history of arterial hypertension and anxiety-depressive disorder. He presented in April 2016 with cough and dyspnea and was diagnosed in May 2016. He was treated at the University Hospital of Split, Croatia.
• Exposure: The article does not report the patient's asbestos exposure history. It describes his treatments: surgery (right extrapleural pneumonectomy), then cisplatin plus pemetrexed, then gemcitabine plus bevacizumab, then pembrolizumab.
• Main results:
  • Surgery and pathology confirmed diffuse epithelioid pleural mesothelioma with mediastinal lymph node involvement, pathological stage pT3N2.
  • After 2 cycles of first-line cisplatin and pemetrexed, the disease progressed.
  • On second-line gemcitabine plus bevacizumab (15 cycles, October 2016 to December 2017), the best response was a partial response. Progression was then found in January 2018.
  • On third-line pembrolizumab (12 cycles in 2018, given every 3 weeks), scans showed a complete response.
  • Pembrolizumab was stopped in November 2018 because of grade 3 pneumonitis, which needed hospital treatment. The patient recovered completely.
  • At the last follow-up, in August 2023, the patient was still in complete remission with no lasting effects of treatment.
  • Tumor tissue showed PD-L1 staining in 2% of tumor cells and a high proportion of cytotoxic CD8+ lymphocytes, along with plasma cells.
  • Genetic testing of the tumor showed it was microsatellite-stable, with a tumor mutational burden of 1 Muts/Mb. It also showed a BAP1 gene alteration (S438) and a PBRM1 gene deletion (exon 19).
• The authors' conclusion: The authors concluded that some patients whose disease does not respond to the best first-line chemotherapy can still benefit greatly from second-line chemotherapy with an antiangiogenic agent, and especially from immunotherapy, even late in treatment. They also concluded that better predictive biomarkers are needed.
• Limitations the authors state:
  • The authors stated that the role of the tumor's immune cell environment in the response to immunotherapy requires further investigation.

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Pleural Mesothelioma, Neoplasm, Median Overall Survival, Prognosis, Unresectable, Pemetrexed (Alimta), Cisplatin.

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• Complete Pathological Response After Neoadjuvant Chemo-Immunotherapy in Malignant Pleural Mesothelioma — F.T. Tostes, M. Zugman, et al. (2022)
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