MG Patients Have Greater Risk of Other Cancers, Registry Analysis Finds

People with myasthenia gravis (MG), particularly those with late-onset and thymoma-associated MG — disease linked to a tumor in the thymus gland — have a higher risk of developing other types of cancer, according to an analysis of a Swedish national registry.

The results also showed that MG patients treated with corticosteroid-sparing immunosuppressants had a higher cancer risk. 

The study, “Cancer in myasthenia gravis subtypes in relation to immunosuppressive treatment and acetylcholine receptor antibodies: a Swedish nationwide register study,” was published in the European Journal of Neurology.  

A tumor in the thymus gland, or thymoma, is the cause of MG for up to 15% of patients with the neuromuscular condition; meanwhile, up to 50% of thymoma patients develop MG.

Thymus tumors can cause the production of antibodies that target the neuromuscular junction components — the place where nerve cells connect with the muscles they control — which disrupts communication and leads to symptoms. Specifically, two main targets in MG are the acetylcholine receptors, or AChRs, and the muscle-specific kinase protein, called MuSK.

Several studies have described the risk of other cancers in addition to thymoma (extrathymic) in MG patients, but the results have been inconsistent. Additionally, few studies have evaluated cancer risk in people with MG who are treated with immunosuppressant medications. Such medications also can increase cancer risk.

Now, researchers at Uppsala University, in Sweden, have conducted a register-based nationwide study to investigate cancer occurrence in Swedish MG patients. The team also assessed the risks associated with corticosteroid-sparing immunosuppressants (CSIS). These therapies are given to patients to allow for a reduction of corticosteroid use, so as to ease treatment side effects from such medications.

Data were collected from the Swedish National Patient Register (NPR), the Swedish Prescribed Drug Register (SPDR), and the Swedish Cancer Register (CR). Of note, it is mandatory for healthcare providers in Sweden to report newly detected cancer cases to the CR.

The study included 2,812 people with MG, with a nearly even number of men (1,412) and women (1,400). Among the patients, 92 (3%) had juvenile-onset MG (JMG), 632 (23%) had early-onset MG (EOMG), and 1,968 (70%) had late-onset MG (LOMG). Thymoma-associated MG (TAMG) was found in 120 participants (4%).

In all, 691 of the patients (25%) had a cancer diagnosis; 61 individuals had a thymoma only. Of the 945 total cancer diagnoses included in the register, 861 were extrathymic cancers — in addition to thymoma. A total of 527 cancers (61%) were diagnosed before MG, while 199 patients were diagnosed with cancer after MG diagnosis.

The most common other cancers found before the MG diagnosis occurred in the male genital organs, female genital organs, and skin. The cancers diagnosed after MG included skin cancer, cancer in the male genital organs, and cancer in the digestive organs.

Cancer was most frequently found in those with thymoma-associated MG (29%) and late-onset MG (28%). For those with TAMG, the most common extrathymic cancers were those of the female genital organs, skin, and digestive organs. At the same time, people with LOMG had cancers of the male genital organs (mostly in the prostate), skin, the female genital organs, and the digestive organs. 

In early onset MG, 35 patients (5.5%) had a cancer diagnosis, of which 23 occurred before MG. The most frequent cancer type in these individuals occurred in the female genital organs, followed by skin cancer, breast cancer, and cancers of the thyroid or other endocrine glands. Only one JMG patient was diagnosed with cancer.

In MG patients who tested positive for anti-AChR antibodies, 122 (22%) had a cancer diagnosis, while 60 patients (19.5%) who tested negative for these antibodies were diagnosed with cancer. Levels of anti-AChR antibody did not correlate with time to a cancer diagnosis. One anti-MuSK antibody-positive patient had a cancer diagnosis.

CSIS medication was prescribed for 876 patients. Some — 161 patients — had one CSIS therapy, but most of these individuals, 715 in total, had two such therapies. 

The frequency of cancer was significantly lower in those who did not receive CSIS medications than in patients who received two CSIS therapies. More frequent cancers occurred in the digestive organs, male genital organs, and the skin. Other cancers did not differ between patients who did and did not receive CSIS. 

The immunosuppressant azathioprine was given to 745 patients (26.5%). More of those who received one or more azathioprine prescriptions developed cancer than participants not treated with this therapy. A similar difference also was found in the LOMG group, with patients with two or more prescriptions having more cancer cases than those not treated with the immunosuppressant.

Azathioprine-treated patients had more melanoma skin cancer and cancer in the digestive organs and male genitalia. The incidence of cancer increased with higher azathioprine exposure time.

Cyclosporine was prescribed to 168 patients, or 6% in all. Treated patients had a significantly higher extrathymic cancer frequency compared with those not treat. Again, the difference also was found in LOMG participants.

“In summary, this nationwide study sheds light on the high frequency of extrathymic cancers in MG subgroups,” the scientists wrote.

“We noted a clear correlation between CSIS exposure, including [azathioprine and cyclosporine], and cancer risk in MG patients,” they wrote.

The researchers noted that a majority of patients had a cancer diagnosis prior to that of MG. That “in part could be due to a longer observation period before MG [diagnosis], however evaluation of other contributing factors is warranted,” they wrote. 

One study limitation, according to the team, was a lack of information regarding MG severity and other forms of treatment. Having data on MG autoantibodies from a limited number of participants was another limitation, they said.