Rheumatic Complications from Immune Checkpoint Inhibitors

Case 3 Continued

The patient’s arthritis is brought under control on adalimumab, and prednisone is tapered off. Can her ICI be resumed?

Resuming ICI

In general, ICI rechallenge is not considered after life-threatening irAEs, such as myocarditis or pneumonitis. A study of patients who had positive tumor responses prior to experiencing a severe event found no difference in cancer outcomes between those who resumed ICI therapy vs. those who permanently discontinued the ICI.²⁶ Thus, ICI resumption may not always be necessary.

Clinicians may consider resuming an ICI once a patient’s irAE has been downgraded to grade 1, requiring minimal immunosuppression (i.e., prednisone equivalent to ≤10 mg).

Results from rechallenge have been mixed, ranging from no recurrence to severe recurrence to completely different irAEs. Recurrence is more common when the original irAE occurred soon after ICI initiation.²⁷ Class switching (e.g., anti-CTLA-4 to anti-PD-1), if appropriate, has also been shown help prevent recurrence in some cases.

If her cancer warrants ongoing treatment, one could consider rechallenging this patient with anti-PD-1 monotherapy with concomitant adalimumab. This decision should be made jointly with the patient and her oncologist.

Other irAEs

In addition to ICI-arthritis, several other rheumatic irAEs can occur with ICI use. ICI-polymyalgia rheumatica is common and can present independently or in conjunction with ICI-arthritis. ICI-sicca is a rarer event, which predominantly involves the mouth rather than the eyes.

ICI-fasciitis is rare, but carries the potential for severe morbidity. It manifests initially as swelling and nonpitting edema of the legs and forearms, causing pain and stiffness, and can progress to severe fibrotic disease if not treated promptly. MRI imaging and/or biopsy can be helpful in making a fasciitis diagnosis.

Vasculitis and sarcoidosis have also been reported as uncommon rheumatic irAEs. Interestingly, systemic lupus erythematosus does not seem to occur as an irAE, although subacute cutaneous lupus does rarely manifest as an irAE.

Regardless of presentation, rheumatologists may be called upon to aid patients and physicians in the management of irAEs, given their autoimmune nature. Symptom recognition, prompt treatment and coordinated care with the oncologist, as well as other specialists, can minimize a patient’s organ damage and improve their quality of life.

Nilasha Ghosh, MD, MS, is a rheumatologist at the Hospital for Special Surgery, New York, and an assistant professor at Weill Cornell Medicine, New York, with special interests in education and the intersection of rheumatology and oncology.

Anne R. Bass, MD, is a rheumatologist at the Hospital for Special Surgery, New York, and a professor of clinical medicine at Weill Cornell Medicine, New York. She leads a multidisciplinary team studying the clinical and biological characteristics of checkpoint inhibitor-associated autoimmunity.

Acknowledgment

We would like to thank Dr. Edward DiCarlo (Hospital for Special Surgery) for providing the histopathology images relevant to this publication.

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