ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 3080

Rheumatologic Consequences of Immunotherapy to Treat Malignancies: The Tip of an Iceberg

Laura Cappelli1, Anna Kristina Gutierrez2, Alan N. Baer2, Jemima Albayda3, Rebecca L. Manno2, Uzma Haque3, Ami A. Shah3, Evan Lipson4, Karen Bleich5, Julie Brahmer4, Patrick Forde4, Dung Le6, Jarushka Naidoo4 and Clifton Bingham III7, 1Medicine/Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 2Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 3Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 4Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 5Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, 6Johns Hopkins University School of Medicine, Baltimore, MD, 7Johns Hopkins University, Baltimore, MD

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: , ,

Session Information

Date: Tuesday, November 15, 2016

Title: Miscellaneous Rheumatic and Inflammatory Diseases II

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Rheumatologic Consequences of Immunotherapy to Treat Malignancies: The Tip of an Iceberg  

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.

 

Disclosure: L. Cappelli, None; A. K. Gutierrez, None; A. N. Baer, Bristol Myers Squibb, 5; J. Albayda, None; R. L. Manno, None; U. Haque, None; A. A. Shah, None; E. Lipson, Bristol-Myers Squibb, 5; K. Bleich, None; J. Brahmer, Bristol-Myers Squibb, 2; P. Forde, Bristol-Myers Squibb, 2,AstraZeneca, 2,Novartis Pharmaceutical Corporation, 2; D. Le, Bristol-Myers Squibb, 2; J. Naidoo, Bristol-Myers Squibb, 5; C. Bingham III, Bristol-Myers Squibb, 5.

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 .

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