Immune-Related Adverse Events in Cancer Patients Treated with Immune Check Point Inhibitors: A Single Center Experience

Taylor Doberstein¹, Aneet Kaur¹, Elizabeth Field² and Namrata Singh³, ¹Internal Medicine, University of Iowa, Iowa City, IA, ²Iowa City VA, Iowa City, IA, ³Internal Medicine, University of Iowa Hospitals and Clinics and Iowa City VA, Iowa City, IA

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Immunotherapy and inflammatory arthritis

Session Information

Date: Tuesday, November 7, 2017

Title: Miscellaneous Rheumatic and Inflammatory Diseases Poster II

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: The immune checkpoint inhibitors (ICIs) anti-CTLA4 (cytotoxic T-lymphocyte associated protein 4) and anti-PD1 (programmed death cell protein 1) have revolutionized cancer treatment. ICIs interrupt immune inhibitory pathways, thereby discharging CD8-mediated killing of cancerous tissue (1). However, ICIs also can provoke powerful autoimmune reactions in other organ systems (2). As ICI use becomes more widespread, more immune-related adverse events (IrAEs) are being reported. Our aim was to investigate the incidence and nature of IrAEs in cancer patients treated with anti-CTLA4 or anti-PD1 at our institution.

Methods: We performed a retrospective chart review of all patients treated for cancer with anti-PD1 (pembrolizumab or nivolumab) or anti-CTLA4 (ipilimumab) at the University of Iowa Hospitals and Clinics between January 2014 to April 2016. Demographic data, cancer type and stage, autoimmune diagnosis and symptoms, and drug treatment information were extracted. IrAEs included any new autoimmune disorder (i.e. inflammatory arthritis) or disease flare of pre-existing autoimmune disorder that occurred after start of ICI treatment.

Results: We identified 220 patients prescribed pembrolizumab, nivolumab, or ipilimumab. Fifteen percent (33/220) developed IrAE, 16 with anti-CTLA4 (Table 1) and 17 with anti-PD1 (Table 2). Two patients on anti-PD1 developed new onset inflammatory arthritis and were successfully treated with corticosteroids and methotrexate. Twelve patients were diagnosed with colitis, 9 with thyroid disorder or worsening of previously stable thyroid disease, 4 with pneumonitis, 2 with hypophysitis, 1 with myasthenia gravis flare, 1 with optic neuritis, 1 with psoriasis flare, and 1 with adrenal crisis. The severity of IrAEs required discontinuation of cancer therapy in 39% of those with IrAEs and 5.9% of all ICIs-treated patients.

Conclusion: Gastrointestinal and thyroid IrAEs were by far the most common, accounting for nearly two-thirds of all IrAEs. Only 2 patients developed inflammatory arthritis, and corticosteroids and methotrexate controlled symptoms in both. Additional studies are needed to determine whether one can maintain more patients on ICI treatment by earlier referral to specialist for appropriate intervention of IrAEs.

Table 1. Patient demographics, cancer type and stage, IrAE reported, and its treatment while on anti-CTLA4

Patient	Gender	Age	Medication Received	Cancer Type	Stage	IRAE Reported	Treatment
1	Male	34	Ipilimumab	Melanoma	IV	Hypothyroidism	Levothyroxine
2	Male	62	Ipilimumab	Melanoma	IV	Hypothyroidism	Levothyroxine
3	Female	63	Ipilimumab	Melanoma	IIIC	Hypothyroidism	Levothyroxine
4	Female	29	Ipilimumab	Melanoma	IIIC	Hypothyroidism	Levothyroxine
5	Female	53	Ipilimumab	Melanoma	IV	Hypophysitis	Corticosteroids, endocrine consult
6	Male	64	Ipilimumab	Melanoma	IV	Hypophysitis	Endocrine consult, levothyroxine, systemic steroids
7	Male	65	Ipilimumab	Melanoma	IV	Adrenal crisis	Corticosteroids
8	Male	52	Ipilimumab	Melanoma	IIIC	Colitis	Corticosteroids, ipilimumab discontinued
9	Male	69	Ipilimumab	Melanoma	IV	Colitis	Corticosteroids, ipilimumab discontinued
10	Male	63	Ipilimumab	Melanoma	IV	Colitis	Corticosteroids, ipilimumab discontinued
11	Male	64	Ipilimumab	Melanoma	IV	Colitis	Corticosteroids
12	Male	58	Ipilimumab	Melanoma	IV	Colitis	Corticosteroids
13	Female	76	Ipilimumab	Melanoma	IV	Colitis	Corticosteroids
14	Male	57	Ipilimumab	Melanoma	IIIC	Colitis	Prednisone, ipilimumab discontinued
15	Male	82	Ipilimumab	Melanoma	IV	Pneumonitis	Corticosteroids, ipilimumab discontinued
16	Female	27	Ipilimumab	Melanoma	IV	Optic neuritis	Corticosteroids

Table 2. Patient demographics, cancer type and stage, IrAE reported, and its treatment while on anti-PD1

Patient	Gender	Age	Medication Received	Cancer Type	Stage	IRAE Reported	Treatment
1	Male	71	Nivolumab	Renal	IV	Inflammatory arthritis	Corticosteroids, Methotrexate
2	Female	67	Pembrolizumab	Melanoma	IV	Inflammatory arthritis	Prednisone, Methotrexate
3	Male	67	Pembrolizumab	Melanoma	IV	Psoriasis flare	Dexamethasone
4	Male	69	Pembrolizumab	Melanoma	IIIC	Hypothyroidism	Levothyroxine
5	Male	50	Pembrolizumab	Melanoma	IV	Hypothyroidism	Levothyroxine
6	Female	71	Nivolumab	Renal	IV	Hypothyroidism	Levothyroxine
7	Female	66	Nivolumab	Lung adenocarcinoma	IV	Autoimmune thyroiditis	Endocrine consult, nivolumab stopped.
8	Male	47	Pembrolizumab	Clear cell sarcoma	IV	Autoimmune thyroiditis	Levothyroxine, endocrine consult
9	Male	76	Pembrolizumab	Melanoma	IV	Myasthenia gravis flare	Corticosteroids, plasmapheresis, pembrolizumab discontinued
10	Male	57	Pembrolizumab	Melanoma	IV	Colitis	GI consult, budesonide, pembrolizumab discontinued
11	Female	45	Nivolumab	Bladder	IV	Colitis	Corticosteroids
12	Female	73	Nivolumab	Melanoma	IV	Colitis	Corticosteroids, budesonide
13	Female	77	Nivolumab	Melanoma	IV	Ulcerative colitis flare	Corticosteroids, nivolumab discontinued after 2^nd flare
14	Male	63	Nivolumab	Melanoma	IV	Colitis	Corticosteroids, nivolumab discontinued
15	Male	65	Nivolumab	Lung adenocarcinoma	IIIA	Pneumonitis	Corticosteroids, nivolumab continued. Nivolumab discontinued after 2^nd flare
16	Female	51	Nivolumab	NSCLC	IV	Pneumonitis	Corticosteroids, nivolumab discontinued
17	Male	60	Nivolumab	Renal	IV	Pneumonitis	Corticosteroids, nivolumab discontinued

Disclosure: T. Doberstein, None; A. Kaur, None; E. Field, None; N. Singh, None.

To cite this abstract in AMA style:

Doberstein T, Kaur A, Field E, Singh N. Immune-Related Adverse Events in Cancer Patients Treated with Immune Check Point Inhibitors: A Single Center Experience [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/immune-related-adverse-events-in-cancer-patients-treated-with-immune-check-point-inhibitors-a-single-center-experience/. Accessed .

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