Use of Immune Checkpoint Inhibitors in Mesothelioma
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.
KeywordsMesothelioma 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.NCCN: NCCN Malignant Pleural Mesothelioma guidelines in https://www.nccn.org/professionals/physician_gls/pdf/mpm_blocks.pdf (ed), 2018.
- 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.• 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.Mansfield AS, Peikert T, Smadbeck JB, et al. Neoantigenic potential of complex chromosomal rearrangements in mesothelioma. J Thorac Oncol. 2018;10.Google Scholar
- 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.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.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
- 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.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