Rheumatologic side effects possible with immunotherapies

Cancer patients taking immunotherapy drugs such as nivolumab (Opdivo) may be more susceptible to developing autoimmune joint and tissue diseases, including inflammatory arthritis.

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This according to a preliminary study by researchers from Johns Hopkins University School of Medicine, Baltimore that was published in the Annals of the Rheumatic Diseases (2017; 76:43-50). In case reports on 13 cancer patients-about 1.3% of the total patients treated with nivolumab and ipilimumab (YERVOY) at the Johns Hopkins Hospital from 2012-2016-the authors observed development of new-onset arthritis or sicca syndrome, a set of autoimmune conditions causing dry eyes and mouth, including Sjogren’s syndrome.

Study author Laura C. Cappelli, MD, of Johns Hopkins University School of Medicine, noted that even though the sample size was small, further research could confirm a cause-and-effect relationship, and she believes the rate is likely an underestimation of how common rheumatologic diseases are in patients taking so-called immune checkpoint inhibitors.

S. Adam Ramin, MD, of Urology Cancer Specialists in Los Angeles, said it’s important to consider that by the time patients undergo immunotherapy, most have developed metastatic disease with poor long-term prognosis.

“Treatment with checkpoint inhibitors has shown tremendous potential in significantly increasing the survival of these patients,” Dr. Ramin told Urology Times.

“We also know that treatments for cancer are associated with varying degrees of side effects. Overall, the benefits of checkpoint inhibitors outweigh their risks of side effects. However, these risks must be weighed against the potential advantages on an individual basis,” added Dr. Ramin, who was not involved with the study.

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In a press release from Johns Hopkins, Dr. Cappelli said she wants the findings to raise awareness that rheumatologic side effects may occur with these drugs.

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“It is important when weighing the risk-benefit ratio of prescribing these drugs. And it’s important for people to be on the lookout for symptoms so they can see a rheumatologist early in an effort to prevent or limit joint damage,” Dr. Cappelli said.

Dr. Ramin noted that there have been developments in new immunotherapy drugs for bladder and kidney cancer, and so understanding the side effects are important for these agents, as well.

The current study did not examine patients receiving atezolizumab (Tecentriq). It did, however, include patients receiving nivolumab, which received FDA approval in November 2015 for the treatment of patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy. Earlier this month, nivolumab was granted FDA approval for treatment of patients with previously treated locally advanced or metastatic urothelial carcinoma. The second drug in the study, ipilimumab, is indicated for the treatment of unresectable or metastatic melanoma.

Immunotherapy is increasingly identified as the best option for a growing number of cancers, many of which were previously intractable. That’s why the American Society of Clinical Oncology and the National Comprehensive Cancer Network are collaborating on practical clinical guidance for the management of side effects caused by immunotherapy.

While these side effects are generally mild and infrequent, when they do occur, they can be serious and even life threatening if not identified and treated in a timely manner.

“It is very conceivable that as the immune system becomes highly activated to attack foreign cells, it may also attack some native cells, especially in the joints,” Dr. Ramin said. “In the future, we will see higher levels of specificity in tailor-made drugs for patients’ malignancies. As our treatments become more targeted, the level of efficacy will increase, while the intensity of side effects will diminish.”

Several of Dr. Cappelli’s co-authors have a financial and/or other relationship with Bristol-Myers Squibb and/or other pharmaceutical companies.

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