Session Title: Miscellaneous Rheumatic and Inflammatory Diseases II
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways are increasingly used to treat multiple malignancies and prolong survival. By activating T-cells, ICIs also cause immune-related adverse events (IRAEs). Rheumatic IRAEs are not well described. We report our initial experiences with ICI-induced inflammatory arthritis, crystalline arthritis and sicca syndrome.
Methods: We report patients seen in Johns Hopkins Rheumatology clinics from 2012-2016 with new rheumatic symptoms during or following treatment with anti-CTLA-4 and/or anti-PD-1 therapy for solid tumors.
Results: We identified 17 patients receiving selected ICIs and developing rheumatic IRAEs (table 1). Mean age was 59.5 years. Cancer types included melanoma, non-small cell lung cancer, small cell lung cancer, colon cancer and renal cell carcinoma. ICI regimens included anti-PD-1 or anti-CTLA-4 monotherapy (n=8) or combination therapy (n=9). Eleven of 17 patients developed 3 subtypes of inflammatory arthritis (RA-like symmetrical polyarthritis, reactive arthritis, oligoarticular large joint arthritis); and 5/5 with arthrocentesis had inflammatory synovial fluid (WBC range 9854-28,400 cells/mm3, >70% PMNs); 5 had confirmatory imaging (3 ultrasound, 1 MRI, 1 CT). RF and CCP were negative in these arthritis patients. Two patients developed new pseudogout or gout confirmed by joint aspiration or dual energy CT. Four patients developed severe sicca with marked salivary hypofunction. Non-rheumatic IRAEs experienced included: pneumonitis, colitis, interstitial nephritis, hypophysitis and thyroiditis. ANAs were positive in 6/17. Corticosteroids were given to 9/11 patients with inflammatory arthritis, several requiring prednisone >1 mg/kg. Three patients required methotrexate and anti-TNF therapy for inflammatory arthritis.
Conclusion: This is the largest series to our knowledge of inflammatory arthritis and the first report of sicca syndrome and crystalline arthritis due to ICIs. These rheumatic IRAEs cause severe symptoms, and arthritis may require significantly higher doses of steroids for management than for usual inflammatory arthritis. As ICIs are increasingly used for a range of malignancies, new cases of rheumatic IRAEs will likely emerge, and rheumatology referrals will increase. Further research is needed to understand mechanisms, determine risks, and develop management algorithms. Table 1: Demographic features, cancer types, and immunotherapy of included patients.
|Patient||Age||Sex||Race||Type of malignancy||Cancer therapy||Rheumatic IRAE||Best overall response (RECIST 1.1)|
|1||58||Male||Caucasian||Renal cell carcinoma||Anti-PD-1 Anti-CTLA-4||Inflammatory arthritis||Stable disease|
|2||46||Female||Caucasian||Melanoma||Anti-PD-1 Anti-CTLA-4||Inflammatory arthritis||Partial response|
|3||62||Male||African American||NSCLC||Anti-PD-1 Anti-CTLA-4||Inflammatory arthritis||Stable disease|
|4||35||Male||Caucasian||Melanoma||Anti-PD-1 Anti-CTLA-4||Inflammatory arthritis||Stable disease|
|5||56||Male||Caucasian||NSCLC||Anti-PD-1||Inflammatory arthritis||Stable disease|
|6||66||Male||Caucasian||Melanoma||Anti-PD-1 Anti-CTLA-4||Inflammatory arthritis||Partial response|
|7||57||Male||Caucasian||Small cell lung cancer||Anti-PD-1 Anti-CTLA-4||Inflammatory arthritis||Partial response|
|8||42||Male||Caucasian||NSCLC||Anti-PD-1 Anti-CTLA-4||Inflammatory arthritis||Partial response|
|9||75||Female||Caucasian||NSCLC||Anti-PD-1||Inflammatory arthritis||Partial response|
|10||60||Female||Caucasian||NSCLC||Anti-PD-1||Inflammatory arthritis||Not measured*|
|11||55||Female||Caucasian||Colon cancer||Anti-PD-1||Inflammatory arthritis||Stable disease|
|12||61||Male||Caucasian||NSCLC||Anti-PD-1||Sicca syndrome||Stable disease|
|13||57||Male||Caucasian||Melanoma||Anti-PD-1 Anti-CTLA-4||Sicca syndrome||Progressive disease|
|14||74||Male||Caucasian||Melanoma||Anti-CTLA-4||Sicca syndrome||Partial response|
|15||74||Female||Caucasian||Melanoma||Anti-PD-1||Sicca syndrome||Tumor regression observed on clinical exam|
|16||71||Male||African American||NSCLC||Anti-PD-1||Crystalline arthritis||Complete response|
|17||62||Male||Caucasian||Melanoma||Anti-PD-1 CD137 agonist||Crystalline arthritis||Complete response|
|*: Not measured at time of submission due to limited amount of time on treatment.|
To cite this abstract in AMA style:Cappelli L, Gutierrez AK, Baer AN, Albayda J, Manno RL, Haque U, Shah AA, Lipson E, Bleich K, Brahmer J, Forde P, Le D, Naidoo J, Bingham C III. Rheumatologic Consequences of Immunotherapy to Treat Malignancies: The Tip of an Iceberg [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/rheumatologic-consequences-of-immunotherapy-to-treat-malignancies-the-tip-of-an-iceberg/. Accessed February 27, 2020.
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