scholarly journals Autoimmune rhabdomyolysis and a multiorgan display of PD-1 inhibitor induced immune related adverse events during treatment of metastatic melanoma

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Hoda Z. Pourhassan ◽  
David Tryon ◽  
Brett Schaeffer ◽  
Hamid Mirshahidi ◽  
John Wong
Keyword(s):  
Adverse Events ◽  
Healthcare Providers ◽  
Poor Clinical Outcome ◽  
Case Presentation ◽  
Immune Mediated ◽  
Programmed Death ◽  
Ligand Interactions ◽  
Programmed Death 1 ◽  
Cancer Types ◽  
Nodular Recurrence

Abstract Background Programmed death-1 (PD-1) inhibitors are among the immunotherapies that have revolutionized our approach to treating several cancers. These novel agents act by blocking PD-1 receptor/PD-1 ligand interactions that would otherwise allow tumor cells to evade host immune destruction by inhibiting response of cytotoxic T-lymphocytes. They are overall well tolerated, though they have been associated with a constellation of immune mediated adverse events (irAEs). Case presentation We present a case of rare nivolumab mediated adverse events in a patient with nodular recurrence of melanoma. The patient presented with rhabdomyolysis and shortly thereafter developed a constellation of immune-mediated organ derangements. This case further demonstrates the utility and effectiveness of steroid therapy in the setting of irAEs despite our patient’s eventual poor clinical outcome. While PD-1 inhibitors have revolutionized the treatment of several cancers, they require vigilance by the clinician for early detection and treatment of uncommon but potentially fatal irAEs. Conclusions PD-1 inhibitors are now widely used in a multitude of cancer types including melanoma, advanced non-small cell lung cancer, metastatic renal cell carcinoma, and Hodgkin lymphoma amongst others. While these agents are often well tolerated, they are associated with a unique profile of immune-related toxicities that can cause significant morbidity and mortality. Education of both patients and healthcare providers is essential for diagnosis and treatment of these adverse events early in their course. This case highlights the uncommon but potentially serious PD-1-associated toxicity of myopathy and rhabdomyolysis along with other organ involvement and is directly applicable to use of these agents in patients with advanced cancers.

scholarly journals A case report of psoriasis flare following immunotherapy: Report of an important entity and literature review

2020 ◽  
Vol 8 ◽  
pp. 2050313X1989770 ◽  
Author(s):  
Anastasia Politi ◽  
Dimas Angelos ◽  
Davide Mauri ◽  
George Zarkavelis ◽  
George Pentheroudakis
Keyword(s):  
Adverse Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Skin Lesions ◽  
Inflammatory Disorder ◽  
Immune Mediated ◽  
Programmed Death ◽  
History Of ◽  
Programmed Death 1 ◽  
Cessation Of Treatment

Immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte–associated antigen-4 and anti-programmed death-1, are a type of cancer immunotherapy approved for late-stage malignancy treatment. However, such therapies often induce immune-related adverse events. During anti-programmed death-1 blockade therapy, the most commonly reported adverse effects are skin toxicities, such as psoriasis—a chronic immune-mediated inflammatory disorder affecting the skin. We present the clinical characteristics of flared psoriasis in one patient under anti-programmed death-1 therapy who was diagnosed with T2N2M0/IIIB squamous lung carcinoma with a history of psoriasis for the past 5 years, exacerbated after the first cycle of nivolumab. After the third cycle, the extensive skin plaques necessitated treatment cessation. Following the discontinuation of anti-programmed death-1 treatment, skin lesions were treated locally. Possibly, anti-programmed death-1 immunotherapy can trigger immune-mediated diseases, such as psoriasis. Physicians should be alert to immune-related adverse events. Continuation or permanent cessation of treatment depends on the severity and reversibility of immune-related adverse events.

Gastrointestinal Immune Related Adverse Events Associated with Programmed-Death 1 Blockade

2017 ◽  
Vol 152 (5) ◽  
pp. S194
Author(s):  
Michael Collins ◽  
Jean-Marie Michot ◽  
François-Xavier Danlos ◽  
Stéphane Champiat ◽  
Charlotte Mussini ◽  
...  
Keyword(s):  
Adverse Events ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals Management of Adverse Events Following Treatment With Anti‐Programmed Death‐1 Agents

2016 ◽  
Vol 21 (10) ◽  
pp. 1230-1240 ◽  
Author(s):  
Jeffrey S. Weber ◽  
Michael Postow ◽  
Christopher D. Lao ◽  
Dirk Schadendorf
Keyword(s):  
Adverse Events ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals αvβ3-integrin regulates PD-L1 expression and is involved in cancer immune evasion

2019 ◽  
Vol 116 (40) ◽  
pp. 20141-20150 ◽  
Author(s):  
Andrea Vannini ◽  
Valerio Leoni ◽  
Catia Barboni ◽  
Mara Sanapo ◽  
Anna Zaghini ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Αvβ3 Integrin ◽  
Primary Tumors ◽  
Effective Strategies ◽  
Immune Mediated ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Β3 Integrin ◽  
Immunotherapy Target ◽  
Immunosuppressive Microenvironment

Tumors utilize a number of effective strategies, including the programmed death 1/PD ligand 1 (PD-1/PD-L1) axis, to evade immune-mediated control of their growth. PD-L1 expression is mainly induced by IFN receptor signaling or constitutively induced. Integrins are an abundantly expressed class of proteins which play multiple deleterious roles in cancer and exert proangiogenic and prosurvival activities. We asked whether αvβ3-integrin positively regulates PD-L1 expression and the anticancer immune response. We report that αvβ3-integrin regulated constitutive and IFN-induced PD-L1 expression in human and murine cancerous and noncancerous cells. αvβ3-integrin targeted STAT1 through its signaling C tail. The implantation of β3-integrin–depleted tumor cells led to a dramatic decrease in the growth of primary tumors, which exhibited reduced PD-L1 expression and became immunologically hot, with increased IFNγ content and CD8+ cell infiltration. In addition, the implantation of β3-integrin–depleted tumors elicited an abscopal immunotherapeutic effect measured as protection from the challenge tumor and durable splenocyte and serum reactivity to B16 cell antigens. These modifications to the immunosuppressive microenvironment primed cells for checkpoint (CP) blockade. When combined with anti–PD-1, β3-integrin depletion led to durable therapy and elicited an abscopal immunotherapeutic effect. We conclude that in addition to its previously known roles, αvβ3-integrin serves as a critical component of the cancer immune evasion strategy and can be an effective immunotherapy target.

scholarly journals Acute kidney injury from immune checkpoint inhibitor use

2019 ◽  
Vol 12 (10) ◽  
pp. e231211 ◽  
Author(s):  
Lexis Gordon ◽  
Pouneh Dokouhaki ◽  
Kimberly Hagel ◽  
Bhanu Prasad
Keyword(s):  
Acute Kidney Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Programmed Death ◽  
Programmed Death 1

Immune checkpoint inhibitors are novel oncological medications, current classes of which include monoclonal antibodies that target inhibitory receptors cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death 1 protein (PD-1) and programmed death-ligand 1. While they are novel in their ability to treat cancer, they also have a unique spectrum of immune-related adverse events. Renal-related immune adverse events, though rare, are an increasingly recognised clinical entity. We present the case of a 67-year-old man with acute kidney injury (AKI) after the second cycle of combination anti-CTLA-4 and anti-PD-1 antibodies for metastatic cutaneous melanoma. He presented with vomiting and diarrhoea, and AKI secondary to dehydration was treated with aggressive rehydration. After failing to recover biochemically, a renal biopsy was performed, which demonstrated severe acute interstitial nephritis. The culprit medications were held and he was treated with steroids. With immunosuppression, creatinine improved to pretreatment values.

scholarly journals High Expression of Pd-1 in Circulating Cells of Patients With Advanced Colorectal Cancer Receiving Adjuvant Therapy

2020 ◽  
Vol 19 ◽  
pp. 153303382096944
Author(s):  
Muhammed A. Bakhrebah ◽  
Mohammad Nasrullah ◽  
Wesam H. Abdulaal ◽  
Mohammed A. Hassan ◽  
Halima Siddiqui ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Adjuvant Therapy ◽  
Tumor Cells ◽  
Immune Cells ◽  
Human Leukocyte ◽  
Genetic Alterations ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Cancer Types

Among all cancer types, colorectal cancer is the third most common in men and the second most common in women globally. Generally, the risk of colorectal cancer increases with age, and colorectal cancer is modulated by various genetic alterations. Alterations in the immune response serve a significant role in the development of colorectal cancer. In primary cancer types, immune cells express a variety of inhibitory molecules that dampen the immune response against tumor cells. Additionally, few reports have demonstrated that classical chemotherapy promotes the immunosuppressive microenvironment in both tissues and immune cells. This study assessed the expression levels of genes using RT-qPCR associated with the immune system, including interferon-γ, programmed death-1, β2-microglobulin, human leukocyte antigen-A, CD3e, CD28 and intracellular adhesion molecule 1, in patients with colorectal cancer, as these genes are known to serve important roles in immune regulation during cancer incidence. Gene expression analysis was performed with the whole blood cells of patients with colorectal cancer and healthy volunteers. Compared with the normal controls, programmed death-1was highly expressed in patients with advanced-stage colorectal cancer. Furthermore, the expression of programmed death-1 was higher in patients receiving adjuvant therapy, which suggests the therapy dampened the immune response against tumor cells. The results of the present study indicate that classical adjuvant therapies, which are currently used for patients with colorectal cancer, should be modulated, and a combination of classical therapy with anti-programmed death-1 antibody should be conducted for improved management of patients with colorectal cancer.

scholarly journals Evolving Concepts: Immunity in Oncology from Targets to Treatments

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Hina Khan ◽  
Rasim Gucalp ◽  
Iuliana Shapira
Keyword(s):  
Cancer Cells ◽  
Immune Checkpoint ◽  
Suppressive Effect ◽  
Anticancer Activities ◽  
Immune Balance ◽  
Immune Mediated ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Immune Ability ◽  
Immune Checkpoint Proteins

Cancer is associated with global immune suppression of the host. Malignancy-induced immune suppressive effect can be circumvented by blocking the immune checkpoint and tip the immune balance in favor of immune stimulation and unleash cytotoxic effects on cancer cells. Human antibodies directed against immune checkpoint proteins: cytotoxic T lymphocytes antigen-4 (CTLA-4) and programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), have shown therapeutic efficacy in advanced melanoma and non-small-cell lung cancer and other malignancies. Immune check point blockade antibodies lead to diminished tolerance to self and enhanced immune ability to recognize and eliminate cancer cells. As a class these agents have immune-related adverse events due to decreased ability of effector immune cells to discriminate between self and non-self. Seventy percent of patients participating in clinical trials have experienced anticancer activities and varying degrees of immune mediated dose-limiting side effects.

An FDA analysis of the association between adverse events and outcome in patients with urothelial cancer receiving a programmed death protein 1 or programmed death ligand 1 (anti-PD-1/L1) antibody.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4549-4549
Author(s):  
Chana Weinstock ◽  
Virginia Ellen Maher ◽  
Laura L. Fernandes ◽  
Shenghui Tang ◽  
Sundeep Agrawal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Urothelial Cancer ◽  
Locally Advanced ◽  
Study Drug ◽  
Drug Approval ◽  
Systemic Corticosteroids ◽  
Immune Mediated ◽  
Programmed Death ◽  
The Relationship

4549 Background: To assess the relationship between tumor response rate, overall survival, and the development of related adverse events of special interest (AESIs) or related immune-mediated adverse events (imAEs) in patients with urothelial cancer treated with anti-PD-1/L1 antibodies. Methods: We examined seven trials that led to drug approval and which included 1747 patients with metastatic or locally advanced urothelial cancer treated with an anti-PD-1/L1 antibody. Five trials enrolled patients who had received prior platinum-based therapy and two enrolled patients who were cisplatin-ineligible. The datasets were searched for AESIs, related AESIs, imAEs, and related imAEs. The relationship to study drug was determined by the Investigator. Immune-mediated adverse events were defined as AESIs treated with topical or systemic corticosteroids. Results: In these exploratory analyses, a related AESI was reported in 64% of responding patients and in 34% of patients who did not respond to the anti-PD-1/L1 antibody while a related imAE occurred in 28% and 12% of patients who did and did not respond to study drug, respectively. In a responder analysis, an increase in overall survival was seen in patients with related AESIs compared to those with no related AESI [hazard ratio (HR) 0.42; 95% CI: 0.37, 0.49]. Fifty-seven percent of responding patients with a related AESI reported a related AESI prior to documentation of response. Conclusions: Patients who responded to treatment with an anti-PD-1/L1 antibody were more likely to report a related AESI or related imAE. This relationship did not appear to be due to the increased duration of exposure in responding patients. Systemic corticosteroid use did not appear to affect the duration of response.

scholarly journals Ramsay-Hunt syndrome and subsequent sensory neuropathy as potential immune-related adverse events of nivolumab: a case report

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Takashi Sakoh ◽  
Mami Kanzaki ◽  
Atsushi Miyamoto ◽  
Sayaka Mochizuki ◽  
Toshiyuki Kakumoto ◽  
...  
Keyword(s):  
Adverse Events ◽  
Sensory Neuropathy ◽  
Ivig Therapy ◽  
Case Presentation ◽  
Varicella Zoster ◽  
Ramsay Hunt Syndrome ◽  
Ataxic Neuropathy ◽  
Hunt Syndrome ◽  
Immune Mediated ◽  
Wide Variability

Abstract Background Nivolumab is an immune checkpoint inhibitor (ICI) and is used for the treatment of advanced non-small cell lung cancer (NSCLC). Several immune-mediated neurological adverse events associated with ICIs have been reported to date, such as Guillain-Barré syndrome. Nivolumab-associated neurological adverse events can vary, and their etiology remains unclear. Case presentation A 72-year-old man with NSCLC was treated with nivolumab as a second-line therapy. After 13 rounds of nivolumab therapy, he presented with Ramsay-Hunt syndrome (RHS) followed by acute ataxic sensory neuropathy. Antiviral therapy for Varicella-Zoster virus and prednisolone resulted in partial improvement of RHS, while almost no recovery was observed in the sensory neuropathy. However, the sensory ataxia significantly improved after intravenous immunoglobulin (IVIg) therapy, and interestingly, the facial palsy associated with RHS also improved. The neurological manifestations, nerve conduction study result, and imaging findings supported that dorsal root ganglia were the primary lesion site of acute ataxic sensory neuropathy. Conclusions Our case presented with the comorbidity of RHS and subsequent ataxic sensory neuropathy after nivolumab therapy to whom IVIg was effective. Our case suggested the wide variability of possible neurological symptoms, and the potential usefulness of IVIg to sensory ataxic neuropathy, seen in cancer patients with ICI treatment.

Sign in / Sign up

Export Citation Format

Share Document