Immune‐Related Hematologic Adverse Events in the Context of Immune Checkpoint Inhibitor Therapy

Immune checkpoint inhibitor therapy (ICIT) is now standard of care for a variety of cancers in both the metastatic and adjuvant settings. As a result, it is imperative to understand the timing, epidemiology, monitoring, diagnosis, and management of immune related adverse events (irAEs) associated with ICIT. This article reviews specific irAEs by organ system, consolidating recommendations from multiple guidelines and incorporating data from case reports to highlight additional evolving therapeutic options for patients. Managing these adverse events requires early recognition, early intervention, and education of both patients and the multidisciplinary health care team. Given the durable responses observed with ICIT, and the irreversible nature associated with some of these irAEs, further research into management of the sequelae of ICIT is required.

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Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease

Journal of Clinical Oncology ◽

10.1200/jco.19.01674 ◽

2020 ◽

Vol 38 (6) ◽

pp. 576-583 ◽

Cited By ~ 23

Author(s):

Hamzah Abu-Sbeih ◽

David M. Faleck ◽

Biagio Ricciuti ◽

Robin B. Mendelsohn ◽

Abdul R. Naqash ◽

...

Keyword(s):

Adverse Events ◽

T Lymphocyte ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Inhibitor Therapy ◽

Checkpoint Inhibitor Therapy ◽

Inflammatory Bowel

PURPOSE The risk of immune checkpoint inhibitor therapy–related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors. PATIENTS AND METHODS We performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events. RESULTS Of the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn’s disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P < .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event–related deaths were recorded. Anti–cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively). CONCLUSION Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.

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Immune checkpoint inhibitor therapy for pediatric cancers: A mini review of endocrine adverse events

Clinical Pediatric Endocrinology ◽

10.1297/cpe.28.59 ◽

2019 ◽

Vol 28 (3) ◽

pp. 59-68 ◽

Cited By ~ 5

Author(s):

Kenji Ihara

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Inhibitor Therapy ◽

Pediatric Cancers ◽

Checkpoint Inhibitor Therapy

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Biomarkers to predict immune-related adverse events with checkpoint inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.8_suppl.131 ◽

2019 ◽

Vol 37 (8_suppl) ◽

pp. 131-131 ◽

Cited By ~ 3

Author(s):

Lia Head ◽

Nicholas Gorden ◽

Robert Van Gulick ◽

Carol M. Amato ◽

Ashley Frazer-Abel ◽

...

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Inhibitor Therapy ◽

Tnf Alpha ◽

Immune Markers ◽

Ifn Alpha ◽

Checkpoint Inhibitor Therapy

131 Background: Immune-related adverse events (IRAE) occur commonly with immune checkpoint inhibitor therapy for the treatment of cancer, although the specific event and severity can vary widely. Little is known regarding factors that may predict which patients will develop an IRAE. The goal of this study is to identify blood biomarkers predictive of IRAE associated with immune checkpoint inhibitor therapy. Methods: Blood samples collected from patients with melanoma prior to receiving therapy with immune checkpoint inhibitors were obtained from the University of Colorado Skin Cancer Biorepository. Testing for a panel of autoantibodies and cytokines (ANA, CCP 3.1, IL-1 beta, IL-2, IL-6, IL-10, IL-12, IP-10, MCP-1, TNF alpha, IFN alpha 2, IFN gamma) in serum samples from patients who had at least one documented IRAE was performed by Exsera BioLabs. Descriptive statistics were used to evaluate biomarker levels in relation to type, grade, and number of adverse events. Results: Pre-treatment samples from 45 patients were evaluated. Median age was 55; 26 were male and 19 were female. The most common IRAEs were colitis (n = 22), thyroid dysfunction (n = 21), and dermatitis (n = 20). Most IRAEs were grade 2 in severity, and the majority of patients (n = 36) experienced more than 1 IRAE. TNF alpha was elevated in 60% of patient samples, while IFN alpha 2 was elevated in 44%. Borderline ANA was detected in 27% of samples and ANA was positive in 11%. No samples had elevation of IL-2. Between 9% and 18% of samples had elevation of the other immune markers tested (IFN gamma, IL-1 beta, IL-6, IL-10, IL-12, and CCP 3.1). Elevation of TNF alpha and IFN alpha 2 were associated with higher grades of IRAEs. No associations between immune markers and the number or type of adverse events in an individual patient were noted. Results from 15 patients who did not have a documented IRAE on immune checkpoint inhibitor therapy are currently pending to confirm these findings are unique to patients developing IRAE. Conclusions: This preliminary data suggests that baseline elevations of TNF alpha and IFN alpha 2 may predict development of IRAEs with immune checkpoint inhibitor therapy. Results from samples from patients who did not develop an IRAE on therapy will be reported at the meeting.

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