scholarly journals Correlative Monitoring of Immune Activation and Tissue Damage in Malignant Melanoma—An Algorithm for Identification of Tolerance Breakage During Immune Checkpoint Inhibitor Therapy of Cancer

2020 ◽  
Vol 21 (6) ◽  
pp. 2020 ◽  
Author(s):  
Renate U. Wahl ◽  
Marike Leijs ◽  
Arturo Araujo ◽  
Albert Rübben
Keyword(s):  
Malignant Melanoma ◽  
Adverse Events ◽  
Immune Activation ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Immune Reaction ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibition ◽  
Checkpoint Inhibitor Therapy

We describe an innovative approach for identification of tolerance breakage during immune checkpoint inhibitor therapy in malignant melanoma. Checkpoint inhibitor therapy enhances the immunologic clearance of cancer by suppressing pathways which induce immune suppression and tolerance. We posit that by analyzing temporal correlations of key markers of immune activation and tissue damage it would be possible to detect the onset of anticancer immune reaction as well as of immunologic adverse effects which might become crucial for optimization as well as safety of immune checkpoint inhibitor treatment. We analyzed time courses of routine laboratory values of serum tumor markers as well as of markers of immune activation in 17 patients with metastasized malignant melanoma receiving checkpoint inhibition and weekly laboratory controls. A parallel serum level increase of interleukin-6 and the tumor marker S100B could be identified in 13 patients, suggesting that the onset of tolerance breakage under checkpoint inhibition may be identified and measured. Immune-related adverse events in the patients were also accompanied by a peak of IL-6. In six patients, the onset of a putative anticancer immune reaction and the beginning of immunologic adverse events occurred in the same treatment cycle; in six patients the immunologic adverse reactions took place in separate cycles.

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

2021 ◽  
Author(s):  
Antoine N. Saliba ◽  
Zhuoer Xie ◽  
Alexandra S. Higgins ◽  
Xavier A. Andrade‐Gonzalez ◽  
Harry E. Fuentes‐Bayne ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy

Systemic Treatment of Cutaneous Adverse Events After Immune Checkpoint Inhibitor Therapy

Dermatitis ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Alexandria M. Brown ◽  
Wylie Masterson ◽  
Jonathan Lo ◽  
Anisha B. Patel
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Systemic Treatment ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy

scholarly journals Diagnosis, monitoring, and management of adverse events from immune checkpoint inhibitor therapy

2019 ◽  
Vol 27 (S2) ◽  
Author(s):  
O.F. Khan ◽  
J. Monzon
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Early Recognition ◽  
Case Reports ◽  
Standard Of Care ◽  
Health Care Team ◽  
Inhibitor Therapy ◽  
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.

scholarly journals Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease

2020 ◽  
Vol 38 (6) ◽  
pp. 576-583 ◽  
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.

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

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 131-131 ◽  
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.

Cures with B-Raf inhibitors as single agents in metastatic B-Raf mutated melanoma: Curb your enthusiasm?

2020 ◽  
pp. 107815522097507
Author(s):  
Constantin A Dasanu
Keyword(s):  
Radiation Therapy ◽  
Malignant Melanoma ◽  
Clinical Outcome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy ◽  
Favorable Clinical Outcome

Development of brain metastases during treatment with B-raf/MEK inhibitors for malignant melanoma tends to be more frequent than during immune checkpoint inhibitor therapy. Long-term responders to B-Raf inhibitors with or without MEK inhibition should be monitored very closely clinico-radiologically for a potential relapse. In addition to surgery and/or radiation therapy, single or dual immune checkpoint inhibitor therapy should be started without delay in this setting to ensure a favorable clinical outcome.

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