Managing the Side Effects of Novel Cancer Immunotherapeutics
Recognising and controlling the adverse effects of CTLA-4 and PD-1 blocking agents
Date: 17 Mar 2014
Topic: Immuno-oncology
In a review article published in the February 2014 issue of Nature Reviews Clinical Oncology, Drs Tara Gangadhar and Robert Vonderheide of the Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA, describe the adverse-event profiles for several novel immune therapy approaches for cancer, and discuss the appropriate management of patients receiving these therapies.
The development of effective immune-based therapy in oncology presents challenges in recognising and managing treatment-related toxic effects. Immune therapies are associated with a variable and unique spectrum of toxic effects, as exemplified by treatment with IL-2 and high-dose interferon. Although most medical oncologists are familiar with their adverse-effect profile, the administration remains limited to specialised centres with experienced and highly-skilled clinical care teams, capable of providing the supportive care required for patients undergoing such therapy, owing to the risk of severe hypotension and organ failure during treatment.
Similarly, several novel immune therapy approaches are currently limited to a few clinical research centres. Therefore, the authors recognise the educational needs and describe in their article the toxicity profiles of agents that block immune checkpoints, immunostimulatory agents, and adoptive T-cell therapy.
http://www.esmo.org/Oncology-News/Manag ... erapeutics
Side effects of the Immunte checkpoint inhibitors
Re: Managing-the-Side-Effects-of-Novel-Cancer-Immunotherapeutics
More articles about side effects:
1. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy.
http://www.ncbi.nlm.nih.gov/pubmed/27085692
Eur J Cancer. 2016 Apr 13
"the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential.
METHODS AND FINDINGS:
In total, 496 patients with metastatic melanoma from 15 skin cancer centers were treated with pembrolizumab or nivolumab; 242 side-effects were described in 138 patients. In 116 of the 138 patients, side-effects affected the skin, gastrointestinal tract, liver, endocrine, and renal system. Rare side-effects included diabetes mellitus, lichen planus, and pancreas insufficiency due to pancreatitis.
CONCLUSION:
Anti-PD1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity."
2. Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy.
http://www.ncbi.nlm.nih.gov/pubmed/27084345
Eur J Cancer. 2016 Apr 12
"the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects can involve skin, gastrointestinal tract, liver, the endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential.
METHODS AND FINDINGS:
In total, 496 patients with metastatic melanoma from 15 skin cancer centres were treated with pembrolizumab or nivolumab. Two hundred forty two side-effects in 138 patients have been analysed. In 77 of the 138 patients side-effects affected the nervous system, respiratory tract, musculoskeletal system, heart, blood and eyes. Not yet reported side-effects such as meningo-(radiculitis), polyradiculitis, cardiac arrhythmia, asystolia, and paresis have been observed. Rare and difficult to manage side-effects such as myasthenia gravis are described in detail.
CONCLUSION:
Anti-PD-1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity."
1. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy.
http://www.ncbi.nlm.nih.gov/pubmed/27085692
Eur J Cancer. 2016 Apr 13
"the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential.
METHODS AND FINDINGS:
In total, 496 patients with metastatic melanoma from 15 skin cancer centers were treated with pembrolizumab or nivolumab; 242 side-effects were described in 138 patients. In 116 of the 138 patients, side-effects affected the skin, gastrointestinal tract, liver, endocrine, and renal system. Rare side-effects included diabetes mellitus, lichen planus, and pancreas insufficiency due to pancreatitis.
CONCLUSION:
Anti-PD1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity."
2. Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy.
http://www.ncbi.nlm.nih.gov/pubmed/27084345
Eur J Cancer. 2016 Apr 12
"the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects can involve skin, gastrointestinal tract, liver, the endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential.
METHODS AND FINDINGS:
In total, 496 patients with metastatic melanoma from 15 skin cancer centres were treated with pembrolizumab or nivolumab. Two hundred forty two side-effects in 138 patients have been analysed. In 77 of the 138 patients side-effects affected the nervous system, respiratory tract, musculoskeletal system, heart, blood and eyes. Not yet reported side-effects such as meningo-(radiculitis), polyradiculitis, cardiac arrhythmia, asystolia, and paresis have been observed. Rare and difficult to manage side-effects such as myasthenia gravis are described in detail.
CONCLUSION:
Anti-PD-1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity."
Olga
Endocrine Side Effects Induced by Immune Checkpoint Inhibitors
Olga
Your response to my calcium post in "diet and lifestyles " spured my curiosity to investigating immune check point inhibitors and their effects on the bones/hormone systens.
Though it appropriate to put under the already established topic.
Unleashing the immune system can and will lead to autoimmune secondarily to the destroying of the cancer tumors.
I feel there needs to be a usage limit?
Endocrine Side Effects Induced by Immune Checkpoint Inhibitors
Context:
In recent years, progress has been made in cancer immunotherapy by the development of drugs acting as modulators of immune checkpoint proteins, such as the cytotoxic T-lymphocyte antigen-4 (CTLA4) and programmed death-1 (PD-1), two co-inhibitory receptors that are expressed on T cells upon activation. These molecules play crucial roles in maintaining immune homeostasis by down-regulating T-cell signaling, thereby preventing unbridled T-cell proliferation while maintaining tolerance to self-antigens, such as tumor-associated antigens. CTLA4 blockade through systemic administration of the CTLA4-blocking antibody ipilimumab was shown to confer significant survival benefit and prolonged stable disease in patients affected by advanced cutaneous melanoma. Other immune checkpoint inhibitors are under clinical evaluation. However, immune checkpoint blockade can lead to the breaking of immune self-tolerance, thereby inducing a novel syndrome of autoimmune/autoinflammatory side effects, designated as “immune-related adverse events,” mainly including rash, colitis, hepatitis, and endocrinopathies.
Data Acquisition:
We searched the medical literature using the words “hypophysitis,” “hypopituitarism,” “thyroid,” “adrenal insufficiency,” and “endocrine adverse events” in association with “immune checkpoint inhibitors,” “ipilimumab,” “tremelimumab,” “PD-1,” and “PD-1-L.”
Evidence Synthesis:
The spectrum of endocrine disease experienced by patients treated with ipilimumab includes most commonly hypophysitis, more rarely thyroid disease or abnormalities in thyroid function tests, and occasionally primary adrenal insufficiency. Hypophysitis has emerged as a distinctive side effect of CTLA4-blocking antibodies, establishing a new form of autoimmune pituitary disease. This condition, if not promptly recognized, may be life-threatening (due to secondary hypoadrenalism). Hypopituitarism caused by these agents is rarely reversible, and prolonged or lifelong substitutive hormonal treatment is often required. The precise mechanism of injury to the endocrine system triggered by these drugs is yet to be fully elucidated.
Conclusions:
Although reports of endocrine side effects caused by cancer immune therapy are abundant, their exact prevalence and mechanism are unclear. Well-designed correlative studies oriented to finding and validating predictive factors of autoimmune toxicity are urgently needed.
Topic: addison's disease,
endocrine system diseases,
signal transduction,
cancer,
adrenal gland hypofunction,
adrenocorticotropic hormone (acth) deficiency,
endocrine system,
homeostasis,
hepatitis,
antigens,
autoantigens,
autoimmunity,
colitis,
exanthema,
hypopituitarism,
immunotherapy,
pituitary diseases,
self tolerance,
thyroid diseases,
thyroid function tests,
t-lymphocyte,
t-lymphocytes, cytotoxic,
antibodies,
thyroid,
tumor antigens,
toxic effect,
malignant melanoma, cutaneous,
drug development,
predictor variable,
medical literature,
adverse event,
tremelimumab,
ipilimumab,
cell cycle checkpoint,
immunotherapy for cancer,
mechanism of injury,
molecule,
immune checkpoint inhibitors,
hypophysitis
Issue Section:
Special features, Special Features - Review
https://academic.oup.com/jcem/article/98/4/1361/2536694
Your response to my calcium post in "diet and lifestyles " spured my curiosity to investigating immune check point inhibitors and their effects on the bones/hormone systens.
Though it appropriate to put under the already established topic.
Unleashing the immune system can and will lead to autoimmune secondarily to the destroying of the cancer tumors.
I feel there needs to be a usage limit?
Endocrine Side Effects Induced by Immune Checkpoint Inhibitors
Context:
In recent years, progress has been made in cancer immunotherapy by the development of drugs acting as modulators of immune checkpoint proteins, such as the cytotoxic T-lymphocyte antigen-4 (CTLA4) and programmed death-1 (PD-1), two co-inhibitory receptors that are expressed on T cells upon activation. These molecules play crucial roles in maintaining immune homeostasis by down-regulating T-cell signaling, thereby preventing unbridled T-cell proliferation while maintaining tolerance to self-antigens, such as tumor-associated antigens. CTLA4 blockade through systemic administration of the CTLA4-blocking antibody ipilimumab was shown to confer significant survival benefit and prolonged stable disease in patients affected by advanced cutaneous melanoma. Other immune checkpoint inhibitors are under clinical evaluation. However, immune checkpoint blockade can lead to the breaking of immune self-tolerance, thereby inducing a novel syndrome of autoimmune/autoinflammatory side effects, designated as “immune-related adverse events,” mainly including rash, colitis, hepatitis, and endocrinopathies.
Data Acquisition:
We searched the medical literature using the words “hypophysitis,” “hypopituitarism,” “thyroid,” “adrenal insufficiency,” and “endocrine adverse events” in association with “immune checkpoint inhibitors,” “ipilimumab,” “tremelimumab,” “PD-1,” and “PD-1-L.”
Evidence Synthesis:
The spectrum of endocrine disease experienced by patients treated with ipilimumab includes most commonly hypophysitis, more rarely thyroid disease or abnormalities in thyroid function tests, and occasionally primary adrenal insufficiency. Hypophysitis has emerged as a distinctive side effect of CTLA4-blocking antibodies, establishing a new form of autoimmune pituitary disease. This condition, if not promptly recognized, may be life-threatening (due to secondary hypoadrenalism). Hypopituitarism caused by these agents is rarely reversible, and prolonged or lifelong substitutive hormonal treatment is often required. The precise mechanism of injury to the endocrine system triggered by these drugs is yet to be fully elucidated.
Conclusions:
Although reports of endocrine side effects caused by cancer immune therapy are abundant, their exact prevalence and mechanism are unclear. Well-designed correlative studies oriented to finding and validating predictive factors of autoimmune toxicity are urgently needed.
Topic: addison's disease,
endocrine system diseases,
signal transduction,
cancer,
adrenal gland hypofunction,
adrenocorticotropic hormone (acth) deficiency,
endocrine system,
homeostasis,
hepatitis,
antigens,
autoantigens,
autoimmunity,
colitis,
exanthema,
hypopituitarism,
immunotherapy,
pituitary diseases,
self tolerance,
thyroid diseases,
thyroid function tests,
t-lymphocyte,
t-lymphocytes, cytotoxic,
antibodies,
thyroid,
tumor antigens,
toxic effect,
malignant melanoma, cutaneous,
drug development,
predictor variable,
medical literature,
adverse event,
tremelimumab,
ipilimumab,
cell cycle checkpoint,
immunotherapy for cancer,
mechanism of injury,
molecule,
immune checkpoint inhibitors,
hypophysitis
Issue Section:
Special features, Special Features - Review
https://academic.oup.com/jcem/article/98/4/1361/2536694
Debbie
Re: Side effects of the Immunte checkpoint inhibitors
Without the risk of scaring all, I feel that an informed patient and care taker is of utmost importance , especially since we all all embarking on a new frontier of cancer treatment.
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Debbie