Use of Immune Checkpoint Inhibitors in Mesothelioma

  • Patrick M. Forde
  • Arnaud Scherpereel
  • Anne S. TsaoEmail author
Lung Cancer (HA Wakelee, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Lung Cancer

Opinion statement

Recent advances in immunology have extended into the mesothelioma field. To date, only Japan has given regulatory approval to salvage nivolumab in chemo-refractory mesothelioma patients. The USA has included in the NCCN guidelines that pembrolizumab (in programmed death ligand 1 (PD-L1) immunohistochemistry (IHC)–positive patients) and nivolumab with or without ipilimumab (whatever the PD-L1 status is) are accepted salvage therapies. Based on the growing body of literature, it is anticipated that checkpoint inhibitors will receive regulatory approval in the USA and Europe soon for salvage therapy. Additional research efforts will determine whether earlier stage patients and frontline unresectable patients will benefit from the addition of immunotherapy to their treatment regimens. The realm of biomarker research has lagged behind in mesothelioma. In general, mesothelioma has less tumor mutation burden than other malignancies. Most of the single-agent salvage checkpoint inhibitor trials have shown a trend correlating higher PD-L1 immunohistochemistry (IHC) with responses. However, survival data remains immature and a larger number of patient outcomes are needed to ascertain the value of PD-L1 IHC as a predictive biomarker. Incorporation of translational studies in all immunotherapy trials and especially window-of-opportunity resectable studies should be supported and instituted in all future mesothelioma trials.


Mesothelioma Immunotherapy Checkpoint inhibitors 


Compliance with Ethical Standards

Conflict of Interest

Patrick M. Forde has received a research funding from AstraZeneca, Bristol-Myers Squibb, Corvus, Kyowa Kirin, and Novartis and has received compensation from AbbVie, Astra Zeneca, Bristol-Myers Squibb, Boehringer Ingelheim, EMD Serono, Inivata, Eli Lilly, Merck, and Novartis for the service on advisory boards and/or as a consultant.

Arnaud Scherpereel has received a research funding (paid to his institution) from Bristol-Myers Squibb and MSD; has received a compensation from AstraZeneca, Bristol-Myers Squibb, MSD, and Roche for participation on advisory boards and/or lectures provided; and has received a travel support to international meetings on thoracic oncology from Bristol-Myers Squibb, MSD, and Roche.

Anne S. Tsao has received a research funding from Bristol-Myers Squibb, Genentech/Roche, Eli Lilly, Millennium, Seattle Genetics, Ariad, Boehringer Ingelheim, Polaris, Epizyme, Merck, AstraZeneca, and Takeda and has received compensation from Bristol-Myers Squibb, Genentech/Roche, Ariad, Boehringer Ingelheim, AstraZeneca, and Takeda for the participation on advisory boards.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    NCCN: NCCN Malignant Pleural Mesothelioma guidelines in (ed), 2018.
  2. 2.
    Weder W, Kestenholz P, Taverna C, Bodis S, Lardinois D, Jerman M, et al. Neoadjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma. J Clin Oncol. 2004;22:3451–7.CrossRefGoogle Scholar
  3. 3.
    Batirel HF, Metintas M, Caglar HB, Yildizeli B, Lacin T, Bostanci K, et al. Trimodality treatment of malignant pleural mesothelioma. J Thorac Oncol. 2008;3:499–504.CrossRefGoogle Scholar
  4. 4.
    Weder W, Stahel RA, Bernhard J, Bodis S, Vogt P, Ballabeni P, et al. Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma. Ann Oncol. 2007;18:1196–202.CrossRefGoogle Scholar
  5. 5.
    Krug LM, Pass HI, Rusch VW, Kindler HL, Sugarbaker DJ, Rosenzweig KE, et al. Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clin Oncol. 2009;27:3007–13.CrossRefGoogle Scholar
  6. 6.
    Flores RM, Akhurst T, Gonen M, Zakowski M, Dycoco J, Larson SM, et al. Positron emission tomography predicts survival in malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2006;132:763–8.CrossRefGoogle Scholar
  7. 7.
    Van Schil PE, Baas P, Gaafar R, et al. Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial. Eur Respir J. 2010;36:1362–9.CrossRefGoogle Scholar
  8. 8.
    Rea F, Marulli G, Bortolotti L, Breda C, Favaretto AG, Loreggian L, et al. Induction chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant hemi-thoracic radiation in malignant pleural mesothelioma (MPM): feasibility and results. Lung Cancer. 2007;57:89–95.CrossRefGoogle Scholar
  9. 9.
    Federico R, Adolfo F, Giuseppe M, Lorenzo S, Martino DPT, Anna C, et al. Phase II trial of neoadjuvant pemetrexed plus cisplatin followed by surgery and radiation in the treatment of pleural mesothelioma. BMC Cancer. 2013;13:22.CrossRefGoogle Scholar
  10. 10.
    Thomas A, Hassan R. Immunotherapies for non-small-cell lung cancer and mesothelioma. Lancet Oncol. 2012;13:e301–10.CrossRefGoogle Scholar
  11. 11.
    Scherpereel A, Astoul P, Baas P, Berghmans T, Clayson H, de Vuyst P, et al. Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. Eur Respir J. 2010;35:479–95.CrossRefGoogle Scholar
  12. 12.
    Woolhouse I, Bishop L, Darlison L, de Fonseka D, Edey A, Edwards J, et al. British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma. Thorax. 2018;73:i1–i30.CrossRefGoogle Scholar
  13. 13.
    Kindler HL, Ismaila N, Armato SG 3rd, et al. Treatment of malignant pleural mesothelioma: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2018;36:1343–73.CrossRefGoogle Scholar
  14. 14.
    Zucali PA, Simonelli M, Michetti G, Tiseo M, Ceresoli GL, Collovà E, et al. Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey. Lung Cancer. 2012;75:360–7.CrossRefGoogle Scholar
  15. 15.
    Scherpereel A, Wallyn F, Albelda SM, Munck C. Novel therapies for malignant pleural mesothelioma. Lancet Oncol. 2018;19:e161–72.CrossRefGoogle Scholar
  16. 16.
    Yap TA, Aerts JG, Popat S, Fennell DA. Novel insights into mesothelioma biology and implications for therapy. Nat Rev Cancer. 2017;17:475–88.CrossRefGoogle Scholar
  17. 17.
    •• Alley EW, Lopez J, Santoro A, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017;18:623–30 Led to the NCCN guidelines to include pembrolizumab as a salvage treatment option for malignant mesothelioma.CrossRefGoogle Scholar
  18. 18.
    • Maio M, Scherpereel A, Calabro L, et al. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial. Lancet Oncol. 2017;18:1261–73 First large trial of a CTLA-4 inhibitor in salvage mesothelioma which did not show a survival benefit over placebo.CrossRefGoogle Scholar
  19. 19.
    Mansfield AS, Peikert T, Smadbeck JB, et al. Neoantigenic potential of complex chromosomal rearrangements in mesothelioma. J Thorac Oncol. 2018;10.Google Scholar
  20. 20.
    Quispel-Janssen J, van der Noort V, de Vries JF, Zimmerman M, Lalezari F, Thunnissen E, et al. Programmed death 1 blockade with Nivolumab in patients with recurrent malignant pleural mesothelioma. J Thorac Oncol. 2018;13:1569–76.CrossRefGoogle Scholar
  21. 21.
    •• Nakano T, Okada M, Kijima T, et al. Long-term efficacy and safety of nivolumab in second- or third-line Japanese malignant pleural mesothelioma patients (phase II: MERIT study). , in IASLC (ed): 19th IASLC World Conference on Lung Cancer Toronto, Canada, 2018. Led to regulatory approval in Japan for nivolumab in salvage therapy for malignant mesothelioma. Google Scholar
  22. 22.
    Desai A, Karrison T, Rose B, et al. Phase II trial of pembrolizumab (NCT02399371) in previously treated malignant mesothelioma: final analysis., in IASLC (ed): 19th IASLC World Conference on Lung Cancer Toronto, Canada, 2018.Google Scholar
  23. 23.
    Hassan R, Thomas A, Nemunaitis JJ, Patel MR, Bennouna J, Chen F, Delord JP, Dowlati A, Kochuparambil ST, Taylor MH, Powderly JD, Vaishampayan UN, Verschraegen CF, Grote HJ, von Heydebreck A, Chin KM, Gulley JL. Phase 1b study of avelumab in advanced previously treated mesothelioma: long-term follow up from the JAVELIN solid tumor study. In Oncology JoC (ed): ASCO. Chicago, Illinois, 2018.Google Scholar
  24. 24.
    Calabro L, Morra A, Giannarelli D, et al. Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2 study. Lancet Respir Med. 2018;6:451–60.CrossRefGoogle Scholar
  25. 25.
    •• Scherpereel A MJ, Greillier L, et al. Second- or third-line nivolumab or nivolumab plus ipilimumab in malignant pleural mesothelioma patients: results of the IFCT-1501 MAPS2 randomised non-comparative phase 2 trial. Lancet Oncol in press, 2018. Led to the inclusion of nivolumab with and without ipilimumab in salvage therapy for malignant mesothelioma. Google Scholar
  26. 26.
    Disselhorst MJQ-JJ, Lalezari F, et al. Phase II trial of nivolumab and ipilimumab in patients with malignant mesothelioma: Lancet Respir Med in press; 2018.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Patrick M. Forde
    • 1
  • Arnaud Scherpereel
    • 2
    • 3
  • Anne S. Tsao
    • 4
    Email author
  1. 1.Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins UniversityBaltimoreUSA
  2. 2.Pulmonary and Thoracic Oncology DepartmentUniv Lille, CHU Lille, INSERM U1189 OncoThAILilleFrance
  3. 3.French National Network of Clinical Expert Centers for Malignant Pleural Mesothelioma Management (MESOCLIN)LilleFrance
  4. 4.Department of Thoracic/Head and Neck Medical OncologyUniversity of Texas M.D. Anderson Cancer CenterHoustonUSA

Personalised recommendations