Background/Purpose:   The introduction of immunotherapy with biologic agents targeting immunologic checkpoints (i.e. CTLA4 and PD-1/PDL-1) have yielded impressive gains for cancer patients. These agents exploit suppressor and regulatory pathways boosting integrated immunity against tumors but are attended by a spectrum of immune related adverse events (irAEs) most notably affecting dermatologic, pulmonary, gastrointestinal and endocrine systems. Reports of rheumatic complications have been sparse and not systematically reported. We have developed a multidisciplinary virtual clinic to evaluate and manage irAEs and now report our initial findings.

Methods:   In February 2016 an interdisciplinary group was created to manage irAEs resulting from patients on approved and experimental immune based therapies for cancer. Patients were identified by treating oncologist and then triaged by a designated advanced practitioner and seen in a facilitated fashion. Two designated rheumatologists saw all patients. A detailed retrospective review of the EMR was performed, including: gender, date of birth, age at diagnosis of malignancy, type and stage of malignancy, prior treatment (chemotherapy, radiation, surgery), checkpoint inhibitor (drug(s), date started, date of last dose), pre-existing autoimmune history, nosology of irAE (type, date of onset, diagnostic testing), irAE treatment and global response to treatment, prior autoimmune serologies.

Results:   IrAEs were evaluated in 12 patients. 9 had no pre-existing autoimmune disease (AID) and 3 with AID (2 rheumatoid arthritis, 1 psoriatic arthritis) were evaluated pre-emptively prior to starting immunotherapy. In the group without AID average age at rheumatologic evaluation was 61.2 years. 5 patients had melanoma, 2 lung adenocarcinoma and 2 renal cell. All had previous treatments with either surgery, chemotherapy, radiation or in combination. Rheumatic irAEs included 4 inflammatory arthritis, 2 polymyalgia rheumatica, 5 sicca and 1 myositis. The majority of patients had more than one irAE, including hypophysitis, thyroiditis and rash. With the exception of one patient who experienced irAE 1 year after starting immunotherapy, the average time to irAE was 52 days. Rheumatic irAEs led to holding of immunotherapy in all but one patient. All cases were treated with glucocorticoids, and 3 required additional therapy with anti-tumor necrosis alpha, intravenous immunoglobulin or hydroxychloroquine. Treatment of irAEs led to significant improvement in 5 patients and only moderate improvement in 3. The lone patient with myositis developed life-threatening muscle involvement requiring hospitalization for aggressive immunosuppression. Of the 3 patients with pre-established AID, 2 experienced flares of their disease after starting immunotherapy.

Conclusion:   Attendant to immunotherapy for malignancy are a growing number of newly defined rheumatic complications. These complications may require aggressive immunosuppression or even cessation of immunotherapy. The epidemiology, natural history and pathophysiology remains undefined. Rheumatologists must be increasingly aware of this spectrum so they may participate in optimal management.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rheumatic-immune-related-adverse-events-of-checkpoint-therapy-for-cancer-case-series-of-a-new-nosologic-entity/