Myasthenia Gravis Potential Result of Cancer Treatment

There is a higher risk of developing myasthenia gravis (MG) with the use of immune checkpoint inhibition (ICI) as a cancer treatment regimen, according to new research published in Cancer Medicine. Because of this, study investigators recommended that treating clinicians be aware of the risk factors for developing MG and continuously monitor their patients for the condition’s development.

“While ICIs can kill tumor cells, they can also overactivate immune cells, leading to immune-related adverse events (irAEs),” they wrote. “ICI-related MG is a life-threatening irAE that appears early in ICI treatment. It has low specificity of symptoms, acute onset, and rapid progress, making early diagnosis and intervention critical.”

Myasthenia Gravis blood test in medical laboratory | Image Credit: luchschenF - stock.adobe.com

For their analysis, statistical significance for MG was defined as having 3 or more reports of the chronic autoimmune neuromuscular condition’s development following treatment, a proportional reporting odds ratio (PRR) of at least 2, and chi-square (χ²) of 4 or more. Outcomes of MG, myasthenic syndrome, and MG crisis were investigated in connection with durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, and AE reports came from the US FDA Adverse Event Reporting System for Q1 2004 through Q3 2022.

The most AEs were seen with nivolumab (380) and pembrolizumab (276) compared with atezolizumab (78), ipilimumab (53), durvalumab (36), and avelumab (5). For death as an outcome, the highest rate of 34.04% was seen in connection with atezolizumab; disability was most common with avelumab, 14.28%; hospitalization (initial or prolonged) from pembrolizumab, 72.02%; life-threatening medical event from nivolumab, 37.00%; and other serious medical events from nivolumab, 95.66%.

Most patients in this analysis were aged 45 to 79 years, with the durvalumab, nivolumab, and ipilimumab groups each having more than 50% of patients aged 65 to 79 years. Excepting the avelumab group, most patients in each ICI group were male patients.

For myasthenic syndrome, the PRRs for each of the immunosuppressants were as follows:

• Pembrolizumab: 44.17 (χ² = 1313.98)
• Nivolumab: 32.09 (χ² =1229.54)
• Durvalumab: 27.83 (χ² = 102.66)
• Atezolizumab: 26.20 (χ² = 235.67)
• Ipilimumab: 21.31 (χ² = 151.15)
• Avelumab: 0

For MG, pembrolizumab again had the highest PRR (39.32; χ² = 7945.15), followed by nivolumab (26.93; χ² = 6636.45), durvalumab (24.21; χ² = 682.04), atezolizumab (18.34; χ² = 900.27), ipilimumab (15.69; χ² = 54.77), and avelumab (14.73; χ² = 566.47).

MG crisis had the fewest reports, seen among those taking pembrolizumab (16.54; χ² = 225.23) and nivolumab (9.20; χ² = 119.14). No data were seen for durvalumab, atezolizumab, avelumab, or ipilimumab.

Median onset of MG was shortest with ipilimumab (1 [range, 1-20] days), followed by pembrolizumab (12 [range, 1-28] days), nivolumab (16 [range, 1-29] days), durvalumab (29 [range, 2-43] days), atezolizumab (48 [range, 11-169] days), and avelumab (64 [range, 21-645] days). However, atezolizumab had the longest range from treatment initiation to MG onset, and 1 to 955 days, and durvalumab, had the shortest range, at 1 to 63 days.

Overall, myasthenia crisis had the highest risk signal with pembrolizumab and nivolumab, and myasthenia syndrome, pembrolizumab. All 6 ICIs, however, can lead to MG, the study investigators concluded, and the strong risk signal strength of pembrolizumab warrants extra attention in the treatment setting for that medication.

The investigators caution that their findings should not be interpreted as recommending against the use of ICIs in combination, but that “clinicians should be vigilant and closely monitor patients for any adverse effects when using these drugs in combination.” It’s especially important, they added, to monitor elderly patients (> 80 years) because melanoma and non–small cell lung cancer are more common in this patient population, and those cancers necessitate treatment with pembrolizumab and nivolumab.

Further research is needed to both inform future treatment decisions and mitigate risk of MG.

“Early identification and treatment of clinical manifestations related to MG are crucial in reducing the occurrence of myasthenia crisis, mortality, disability rate, and prolonged hospitalization,” the study authors concluded. “Therefore, early recognition of MG is a critical step toward developing evidence-based treatment algorithms that can improve clinical outcomes.”

Reference

Kong Q, Wang H, Ren X, Zhuo Y, Peng J. Analysis on the risk of myasthenia gravis related to immune checkpoint inhibitors based on the US FDA Adverse Event Reporting System. Cancer Med. 2023;12(19):19491-19499. doi:10.1002/cam4.6559