Nivolumab resulting in persistently elevated troponin levels despite clinical remission of myocarditis and myositis in a patient with malignant pleural mesothelioma: case report

Our plain-English summary of Nivolumab resulting in persistently elevated troponin levels despite clinical remission of myocarditis and myositis in a patient with malignant pleural mesothelioma: case report, by G. Lie, A. Weickhardt, L. Kearney, et al (Translational Lung Cancer Research, 2020).

The study

• Authors: G. Lie, A. Weickhardt, L. Kearney, Q. Lam, T. John, D. Liew, S. Arulananda
• Journal: Translational Lung Cancer Research
• Published: 2020;9(2):360-365
• Type of article: Case report
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) remains a deadly disease with limited therapeutic options beyond platinum/pemetrexed chemotherapy. Immune checkpoint inhibitors have demonstrated modest benefit in the second to later-line settings. An MPM patient from our institute developed myocarditis and myositis after 2 cycles of second-line nivolumab. Despite immunosuppression with corticosteroids and mycophenolate mofetil, there was ongoing rise in troponin levels which remained elevated for months. The patient developed an impressive but brief response following cessation of nivolumab. Myocarditis and myositis are rare complications of immune checkpoint inhibitors. Clinicians should be aware of these possible complications as myocarditis can result in mortality.

2020 Translational Lung Cancer Research. All rights reserved.

In plain English

This case report described one patient at the authors' institution in Heidelberg, Australia: a 79-year-old retired carpet factory worker with a history of asbestos exposure, diagnosed in August 2017 with right-sided epithelioid malignant pleural mesothelioma. After chemotherapy and later disease progression, the patient was given the immunotherapy drug nivolumab. After two cycles, the patient came to the emergency department with severe weakness. Tests showed a creatine kinase (a muscle damage marker) of 6,602 units/L and a high-sensitivity troponin T (a heart damage marker) of 1,072 ng/L. Immune-related myositis and myocarditis were diagnosed and treated with corticosteroids and mycophenolate mofetil. Weakness and creatine kinase improved quickly. Troponin T, however, rose to 1,728 ng/L by day 13 and stayed raised for months (79 ng/L at 14 weeks), without heart symptoms. Cardiac MRI was consistent with myocarditis. A scan showed near complete metabolic remission of the cancer, but the disease progressed within 3 months. The authors concluded that patients presenting with myositis should be screened for heart involvement even without symptoms.

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 (single patient)
• Who was studied: One 79-year-old retired carpet factory worker with right-sided PD-L1 negative epithelioid malignant pleural mesothelioma, diagnosed August 2017, treated at the authors' institution in Heidelberg, Australia
• Exposure: Treatment studied: nivolumab immunotherapy (3 mg/kg) given as second-line treatment after carboplatin and pemetrexed chemotherapy. The patient's history included asbestos exposure, with no fiber type or details given.
• Main results:
  • After two cycles of nivolumab, the patient presented with severe proximal limb and truncal weakness. Creatine kinase was 6,602 units/L (reference 20 to 200 units/L) and high-sensitivity troponin T was 1,072 ng/L (reference under 15 ng/L).
  • Muscle biopsy showed necrotizing myositis. By day 7 of treatment, creatine kinase had fallen to 446 units/L, but troponin T remained high at 644 ng/L.
  • By day 13, troponin T had risen to 1,728 ng/L while creatine kinase fell to 295 units/L. The patient had no symptoms, and cardiac MRI was consistent with myocarditis.
  • Creatine kinase was in the low-normal range after 3 weeks. Troponin T stayed elevated at 290 ng/L at 4 weeks, 200 ng/L at 8 weeks and 79 ng/L at 14 weeks.
  • A restaging PET/CT after 2 cycles of nivolumab showed near complete metabolic remission. Nivolumab was not restarted because of subclinical myocarditis.
  • The remission was not sustained. A PET/CT 3 months after the last nivolumab dose showed progression, and the disease progressed further on third-line vinorelbine chemotherapy.
• The authors' conclusion: The authors concluded that closer monitoring of cardiac troponin in patients on immune checkpoint inhibitors may help identify subclinical myocarditis. They also concluded that patients presenting with myositis should be screened for cardiac involvement even without symptoms.
• Limitations the authors state:
  • The rise in troponin may have come from regenerating skeletal muscle cells, although the authors said this is infrequently of this magnitude.
  • Repeated cardiac MRI or a heart biopsy might have allowed better correlation with the blood test findings.

Topics

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Pleural Mesothelioma, Pemetrexed (Alimta), Chemotherapy, checkpoint inhibitors.

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