Published: 4 December 2025

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Consider Triple M overlap syndrome (Myocarditis, Myositis and Myasthenia gravis) with immune checkpoint inhibitors

Published: 4 December 2025
Prescriber Update 46(4): 65–66
December 2025

There is increasing awareness of Triple M overlap syndrome, and cases have been reported in New Zealand in association with immune checkpoint inhibitors (ICIs).

Immune checkpoint inhibitors

ICIs are monoclonal antibodies that improve the immune response to tumour cells by increasing T-cell activity.¹ As a result, T-cell mediated attack can also occur on healthy cells, causing immune-mediated adverse reactions in multiple organ systems.¹

ICIs approved in New Zealand include atezolizumab (Tecentriq), durvalumab (Imfinzi), ipilimumab (Yervoy), nivolumab (Opdivo) and pembrolizumab (Keytruda). ICIs are indicated for the treatment of several cancers.

Triple M overlap syndrome

Myocarditis, myositis and myasthenia gravis are immune-mediated adverse reactions known to occur with ICIs.^2-6 These reactions can occur separately, or sometimes together as a triad, known as Triple M overlap syndrome (or myocarditis-myositis-myasthenia gravis overlap syndrome).^7,8

Triple M overlap syndrome varies in presentation and severity. Although rare, it can be life-threatening,^7,8 with in-hospital mortality rates approaching 40%.⁸

Prompt recognition and early treatment of Triple M overlap syndrome is vital. If any one of myocarditis, myositis or myasthenia gravis is suspected in a patient receiving an ICI, check for other autoimmune conditions.⁷

New Zealand case reports

As of 30 September 2025, there were three case reports of patients experiencing concurrent myasthenia gravis, myositis and myocarditis associated with an ICI.

Of these three cases:

• ipilimumab and nivolumab were the suspect medicines in one case (report ID: NZ-Medsafe-162153)
• pembrolizumab was the suspect medicine in two cases (NZ-Medsafe-156395, NZ-Medsafe-161059).

Further information

See the following for more information on ICIs and immune-mediated adverse reactions:

• Autoimmune complications of immunotherapy – Prescriber Update June 2023
• Medicine data sheets

References

1. New Zealand Formulary (NZF). 2025. NZF v160: Immune checkpoint inhibitors 1 October 2025. URL: nzf.org.nz/nzf_70778 (accessed 30 October 2025).
2. Roche Products (New Zealand) Limited. 2025. Tecentriq New Zealand Data Sheet 29 July 2025. URL: www.medsafe.govt.nz/profs/Datasheet/t/Tecentriqinf.pdf (accessed 30 October 2025).
3. AstraZeneca Limited. 2025. Imfinzi New Zealand Data Sheet 17 July 2025. URL: www.medsafe.govt.nz/profs/Datasheet/i/imfinziinf.pdf (accessed 30 October 2025).
4. Bristol-Myers Squibb (NZ) Limited. 2024. Yervoy New Zealand Data Sheet 25 July 2024. URL: www.medsafe.govt.nz/profs/Datasheet/y/yervoyinj.pdf (accessed 30 October 2025).
5. Bristol-Myers Squibb (NZ) Limited. 2025. Opdivo New Zealand Data Sheet 18 September 2025. URL: www.medsafe.govt.nz/profs/Datasheet/o/opdivoinf.pdf (accessed 30 October 2025).
6. Merck Sharp & Dohme (New Zealand) Limited. 2025. Keytruda New Zealand Data Sheet 11 August 2025. URL: www.medsafe.govt.nz/profs/Datasheet/k/Keytruda.pdf (accessed 30 October 2025).
7. Aggarwal N, Bianchini D, Parkar R, et al. 2024. Immunotherapy-induced overlap syndrome: Myositis, myasthenia gravis, and myocarditis – A case series. Case Reports in Medicine  2024: 5399073. DOI: 10.1155/2024/5399073 (accessed 1 October 2025).
8. Furlepa M, Watts I, Carr A. 2025. Management of Triple M syndrome: A narrative review of immune checkpoint inhibitor-induced myasthenia gravis, myositis and myocarditis. Cancers 17(13): 2063. DOI: 10.3390/cancers17132063 (accessed 1 October 2025).