CAR T cells show promise in mesothelioma

Our plain-English summary of CAR T cells show promise in mesothelioma, by D. Killock (Nature Reviews. Clinical Oncology, 2021).

The study

• Author: D. Killock
• Journal: Nature Reviews. Clinical Oncology
• Published: 2021;18(9):541
• Type of article: Comment
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

This one-page research highlight in Nature Reviews Clinical Oncology summarized a phase I trial reported by Adusumilli and colleagues in Cancer Discovery. It is not the original trial report, and it says nothing about asbestos exposure. In the trial, 35 patients with previously treated malignant pleural mesothelioma, or with pleural metastases from lung or breast cancer, underwent apheresis. Of these, 27 received chimeric antigen receptor (CAR) T cells targeting mesothelin, infused into the pleural space. Among 23 patients with mesothelioma who received cyclophosphamide conditioning, median overall survival after infusion was 17.7 months. Eighteen of them also received pembrolizumab, and their median overall survival was 23.9 months. Only two partial responses were seen on imaging. No dose-limiting toxicities were reported. A trial investigator cautioned that this was a phase I trial and that patients were selected because they had to wait a median of 3.2 months for cell manufacturing. The author wrote that comparative trials are likely to be required to clarify the benefits over immune-checkpoint blockade alone, given the high costs.

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: Research highlight (short news summary) of a first-in-human phase I dose-escalation trial; not the original trial report
• Who was studied: 35 patients with previously treated malignant pleural mesothelioma (MPM) or pleural metastases from lung or breast cancer underwent apheresis, and 27 received the infusion. The efficacy-evaluable cohort was 23 patients with MPM who received cyclophosphamide conditioning. Location and dates are not given.
• Exposure: No asbestos or fiber exposure is discussed. The intervention studied was an intrapleural infusion of mesothelin-targeted CAR T cells (dose printed as '0.3−60 × 106 per kg'), with pembrolizumab given to 18 of the 23 efficacy-evaluable patients.
• Main results:
  • In the 23 efficacy-evaluable MPM patients who received cyclophosphamide conditioning, median overall survival after cell infusion was 17.7 months
  • In the subgroup of 18 of these patients who also received pembrolizumab, median overall survival was 23.9 months
  • Objective radiological responses were limited to two partial responses
  • No dose-limiting toxicities were reported. There was no cytokine-release syndrome or neurotoxicity above grade 2, and no on-target, off-tumour toxicities.
• The authors' conclusion: The highlight's author wrote that comparative trials are likely to be required to clarify the benefits of CAR T cell therapy over immune-checkpoint blockade alone, given its high costs. A phase II portion testing the combination with pembrolizumab is ongoing.
• Limitations the authors state:
  • The trial investigator noted that this was a phase I trial and that patients were selected owing to the requirement to wait a median of 3.2 months for CAR T cell manufacturing
  • Most efficacy-evaluable patients (18 of 23) also received pembrolizumab, so survival cannot be attributed to CAR T cells alone

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.

Related studies

• Novel cell imaging techniques show induction of apoptosis and proliferation in mesothelial cells by asbestos — J.L. Goldberg, C.L. Zanella, et al. (1997)
• Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed — L. Cortes-Dericks, G.L. Carboni, et al. (2010)
• Rat pleural mesothelial cells show damage after exposure to external but not internal cigarette smoke — H.S. Sekhon, B. Keeling, et al. (1993)
• Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study — C.A. Poland, R. Duffin, et al. (2008)
• Cancer and inflammation: promise for biologic therapy — S. Demaria, E. Pikarsky, et al. (2010)
• Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future — F. Nicolini, M. Bocchini, et al. (2019)

Browse more research in Nature Reviews. Clinical Oncology, or return to medical research.