PD-1/PD-L1 Checkpoint Inhibitor Immunotherapy for Malignant Pleural Mesothelioma: Case Series and Literature Review

Our plain-English summary of PD-1/PD-L1 Checkpoint Inhibitor Immunotherapy for Malignant Pleural Mesothelioma: Case Series and Literature Review, by M. Zhou, N. Joshi, K.P. Raj, et al (Clinical Lung Cancer, 2021).

The study

• Authors: M. Zhou, N. Joshi, K.P. Raj, H. Wakelee, J.W. Neal
• Journal: Clinical Lung Cancer
• Published: 2021;22(3):e329-e335
• Type of article: Review
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Study design: A retrospective, single-center, case series Introduction: Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm with poor prognosis. The combined cisplatin/pemetrexed regimen is the only regimen currently approved by the FDA. Immunotherapy with checkpoint inhibitors and other therapeutics are quickly becoming the preferred second-line therapy following incorporation into clinical practice guidelines in 2018 as a salvage therapy. Purpose of the study: To describe the use of PD-1/PD-L1 targeted therapy to manage MPM. Methods: Retrospective chart review of patients with MPM treated at a single institution with pembrolizumab or nivolumab was performed. Clinical and pathologic information were extracted and clinical response rate and other outcomes were assessed. Results: Twelve patients received pembrolizumab, and two patients received nivolumab. Patients were 43% male (6 out of 14), 64% non-Hispanic white (9 out of 14), and 93% epithelioid histological subtype (13 out of 14). Prior to immunotherapy, 36% had received surgical resection (5 out of 14), 36% had received radiotherapy (5 out of 14), and 93% received platinum-pemetrexed based chemotherapy (13 out of 14). Objective response rate was 21% (0 CR and 3 PRs), and disease control rate was 43% (3 PRs and 3 SDs). Time to progression ranged from <1 month to 19 months. Conclusion: Based on this small series, real-world PD-1/PD-L1 targeted therapy appears to be a promising treatment for patients with MPM who have disease progression on systemic chemotherapy, consistent with small single arm clinical trials. Further investigation with multicenter, prospective longitudinal cohorts and/or randomized clinical trials may help identify which patients have the largest magnitude of benefit.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

In plain English

This article combined a retrospective case series from Stanford with a review of other clinical trials. The authors reviewed the charts of 14 adults with malignant pleural mesothelioma, aged 48 to 92 at diagnosis, who were treated with pembrolizumab (12 patients) or nivolumab (2 patients) between December 2015 and June 2019. Thirteen had the epithelioid subtype, and all had received chemotherapy first. The patients' asbestos exposure was not reported. Responses were judged retrospectively from scans and notes, without confirmation scans. On that basis, 3 of 14 patients (21%) had a partial response and none had a complete response. With 3 more showing stable disease, the disease control rate was 43%. Time to progression ranged from less than 1 month to 19 months. All 4 patients tested for PD-L1 were negative. The authors concluded that, in this small series, the therapy appears promising for patients whose disease progressed on chemotherapy, with results similar to earlier phase I and II trials. They listed few patients, a retrospective single-site design, and many heavily pretreated patients as limitations.

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-center case series (chart review), followed by a review of published and ongoing clinical trials of immunotherapy in mesothelioma
• Who was studied: 14 adult patients with malignant pleural mesothelioma treated at Stanford between December 2015 and June 2019 (data cutoff November 2019), aged 48 to 92 at diagnosis; 13 of 14 had epithelioid histology
• Exposure: Not an asbestos exposure study. The exposure studied was PD-1 checkpoint inhibitor immunotherapy, given outside clinical trials: pembrolizumab in 12 patients and nivolumab in 2. Patients' asbestos exposure histories were not reported.
• Main results:
  • All 14 patients had received at least one type of systemic chemotherapy before immunotherapy; 13 of 14 (93%) had received platinum-pemetrexed based chemotherapy
  • Time from diagnosis to starting PD-1/PD-L1 therapy ranged from 5 to 84 months
  • Response rate among the 14 patients was 21%: no complete responses and 3 partial responses
  • Disease control rate among the 14 patients was 43% (3 partial responses and 3 with stable disease)
  • Time to disease progression ranged from less than 1 month to 19 months
  • Four patients had PD-L1 testing (1 partial response, 1 stable disease, 2 progression); all 4 tested negative
  • At data cutoff, one patient was still on nivolumab
• The authors' conclusion: The authors concluded that, based on this small series, real-world PD-1/PD-L1 targeted therapy appears to be a promising treatment for MPM patients whose disease progressed on systemic chemotherapy. They said their response and disease control rates were similar to previous phase I and II studies.
• Limitations the authors state:
  • Small number of patients, retrospective review, single site, and many heavily pretreated patients (third line and beyond)
  • PD-L1 and molecular results were available for only a few patients, so no conclusions could be drawn about links between PD-L1 expression or molecular features and response

Topics

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

Medical terms in this study, explained in our Lexicon: PD-1/PD-L1, checkpoint inhibitors, Immunotherapy, Pleural Mesothelioma, Neoplasm, Prognosis, Cisplatin, Pemetrexed (Alimta).

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• Immune checkpoint inhibitor associated reactivation of primary membranous nephropathy responsive to rituximab — J.S. Lin, D.Y. Wang, et al. (2020)
• Exposing Hidden Targets: Combining epigenetic and immunotherapy to overcome cancer resistance — K. Olino, T. Park, et al. (2020)
• Is there a role for immunotherapy in malignant pleural mesothelioma? — A. Tartarone, R. Lerose, et al. (2018)
• Assessment of new HDAC inhibitors for immunotherapy of malignant pleural mesothelioma — D. Bensaid, T. Blondy, et al. (2018)

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