Immunotherapy May Lead to Abnormal Thyroid Function in Patients With Cancer

thyroid cancer

A comprehensive review of patients receiving pembrolizumab at the Mayo Clinic in Rochester, Minnesota, has found an incidence of abnormal thyroid function tests as high as 15%, according to a study presented by Danae Delivanis, MD, at the 15th International Thyroid Congress and 85th Annual Meeting of the American Thyroid Association in Lake Buena Vista, Florida.

Pembrolizumab, an immune checkpoint inhibitor approved to treat melanoma that has metastasized or cannot be surgically removed, as well as non—small cell lung cancer that has metastasized, is known to sometimes cause immune-related adverse events (AEs), often of the thyroid. A greater understanding of the drug is needed to improve patient care. Delivanis et al aimed to comprehensively characterize pembrolizumab-induced thyroid dysfunction and examine its potential pathophysiology.

The team completed a comprehensive retrospective review of 93 patients with cancer receiving pembrolizumab at the Mayo Clinic from March 2014 through January 2015. Most were male.

Delivanis said routine thyroid function testing is recommended for patients on pembrolizumab. The study identified 14 cases of abnormal thyroid function tests, which were examined to determine etiology, incidence, and clinical presentation of the thyroid disorder.

The team defined thyroiditis as suppressed thyroid stimulating hormone (TSH) with an elevated T3 and T4 that progressed or self-resolved. Overt hypothyroidism was defined as an increased TSH and low T4 or T3. Subclinical hypothyroidism was diagnosed when the TSH was increased but the thyroid hormone levels were normal.

Seven patients developed thyroiditis. Four patients experienced new-onset hypothyroidism, and three developed recurrent hypothyroidism requiring a change in the thyroid hormone replacement dose by more than 50%. A total of 12% of the patients, seven of the 57 treated with pembrolizumab, who developed induced thyroid dysfunction were male and seven of 36 or 19% were female. The median age was 58 years of age.

Thirteen of the patients were being treated for metastatic melanoma and one for non—small cell lung cancer. Eleven of the patients had received ipilimumab prior to pembrolizumab. The combination of immune checkpoint blockade may enhance the incidence of thyroiditis/hypothyroidism compared with ipilimumab alone.

The median time to onset of thyroid dysfunction was 6 weeks, after the second cycle of pembrolizumab. Four of the patients, or 29%, had a recovery of thyroid function. Eight of the patients, or 57% did not. And the data was not available about recovery of thyroid function for two cases. Four of the patients developed additional immune-related AEs.

On PET/CT, new thyroid fluorodeoxyglucose (FDG) uptake after pembrolizumab was identified in seven cases, with the median time to increased FDG uptake of 12 weeks.

Thirteen patients had their thyroid peroxidase antibodies (TPO-abs) measured at the time of thyroiditis. Five of them had an elevated titer, with a mean titer of 85 IU/mL.

At baseline anti-TPO ranged from 0.5 IU/mL to more than 800 IU/mL in those five patients. Following treatment with pembrolizumab, the anti-TPO ranged from 0.7 IU/mL to greater than 800 IU/mL.

A patient with new onset thyroiditis had the lowest levels, 0.5 IU/mL and 0.7 IU/mL and a patient with recurrent hypothyroidism had the highest level, at >800 IU/mL, both before and after treatment with pembrolizumab. One patient with subclinical hypothyroidism showed a decrease in anti-TPO following treatment, from 211 IU/mL before treatment to 125 IU/mL after treatment with pembrolizumab.

“Patients with an underlying autoimmune profile are at high risk once started on therapy with pembrolizumab. Checking baseline antibodies may help identify patients at high risk,” said Delivanis.

According to Delivanis, the investigators assume a T-cell—mediated destructive pattern is involved and that comparing healthy volunteers with patients with autoimmune disease may help in understanding the underlying pathophysiology involved.

Delivanis D. Immune therapies targeting the thyroid: new insights from a comprehensive review of pembrolizumab-induced thyroiditis cases at Mayo Clinic. Presented at the 85th Annual Meeting of the American Thyroid Association: Lake Buena Vista, Florida; October 20, 2015. Abstract #88