New Immunotherapies in Oncology Treatment and Their Side Effect Profiles

Sriratana, P.; Norton, Joseph

doi:10.3122/jabfm.2018.04.170387

Cited by 7 publications

(5 citation statements)

References 54 publications

(46 reference statements)

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“…27,28 Nevertheless, pre-existing organ dysfunctions could decompensate during the treatment. [29][30][31] Our patient developed acute CRS after the first intravenous dose of pembrolizumab. A preclinical animal study demonstrated an increase in proinflammatory markers consecutive to a single dose of pembrolizumab in humanised primates with normal cells: these increases in inflammatory markers could explain the manifestations of CRS.…”

Section: Discussionmentioning

confidence: 82%

Acute cytokine release syndrome after a first dose of pembrolizumab as second-line treatment for metastatic, programmed death-ligand 1-positive, non-small-cell lung cancer

Normand

Zender

Staehli

et al. 2020

J Oncol Pharm Pract

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Introduction The use of programmed death-ligand 1 (PD-L1) checkpoint inhibitor therapy is expanding, although its adverse effects are not completely known. We report on a rare case of acute cytokine release syndrome related to pembrolizumab use in a patient with lung cancer. Case report A 79-year-old man with metastatic, PD-L1-positive, non-small-cell lung cancer developed a febrile condition associated with a systemic inflammatory response syndrome and suffered haemodynamic compromise four hours after the first intravenous administration of pembrolizumab. A thorough medical workup found no alternative cause and a grade 2 cytokine release syndrome (CRS) was diagnosed. Management and outcome: Aggressive fluid resuscitation and supportive therapy led to restitutio ad integrum. Discussion Acute CRS after the administration of a PD-L1 inhibitor is infrequent but could be a fatal condition. Supportive treatment and, if necessary, corticosteroids should be considered.

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Section: Discussionmentioning

confidence: 82%

Acute cytokine release syndrome after a first dose of pembrolizumab as second-line treatment for metastatic, programmed death-ligand 1-positive, non-small-cell lung cancer

Normand

Zender

Staehli

et al. 2020

J Oncol Pharm Pract

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“…In a report by Sriratana et al, 14 immune-mediated pneumonitis occurred in 3.4% of patients, type 1 DM was seen in 0.2%, and thyroid dysfunction up to 12.5% in patients receiving PD-L1 therapy more specifically pembrolizumab. Another review of literature by So et al 15 looked at 88 patients with irAE in ipilimumab naive and treated patients with advanced melanoma who received pembrolizumab.…”

Section: Discussionmentioning

confidence: 93%

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab

Kethireddy

Thomas

Bindal

et al. 2020

J Oncol Pharm Pract

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Introduction Immune agents including anti-programmed death receptor-1 and anti-cytotoxic T-lymphocyte antigen-4 have been associated with numerous immune-related complications. Pembrolizumab, a programmed death-1 inhibitor, has been associated with a number of immune-related adverse events such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes. Case report We present a rare case of an elderly male on pembrolizumab who suffered from four autoimmune toxicities including type 1 diabetes, pneumonitis, hypothyroidism, and polymyalgia rheumatica likely catalyzed by age-related immune activation. Management and outcome: Immunotherapy was indefinitely stopped, and patient was started on steroids for the immune-related adverse events with complete resolution of polymyalgia rheumatica. Thyroid dysfunction resolved once he started thyroid replacement therapy. His diabetes is well controlled with insulin and is followed by endocrinology. He continues on prednisone for immune-mediated pneumonitis with a good response with regular monitoring via computed tomography scans and pulmonary consultation. Discussion Few cases wherein multiple toxicities are seen within one patient are reported. Aging appears to be a risk factor for immune-related adverse events. Aging is associated with an increased incidence of autoimmunity as programmed death-1 ligand expression represents an important mechanism that tissues use to protect from self-reactive effector T cells. Programmed death-1 blockade breaks this protective mechanism and enhances autoimmune diseases. Therefore, close monitoring and extreme vigilance is warranted while using immune checkpoint inhibitors including pembrolizumab as multiple toxicities can occur within a short span of infusion, especially in elderly individuals. Prompt discontinuation and the use of a multidisciplinary team are prudent to prevent further morbidity and mortality.

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“…The symptoms were managed by iv. fluid and analgesic and did not require treatment with corticosteroids or cytokine antagonists, which remain the standard of care for cytokine release syndrome observed with some immunotherapy agents [48]. The reason that the hyperactivation of the immune system by some immunotherapy agents [48] has not been observed with GEN-1 is probably due to small changes in blood levels of immunocytokines.…”

Section: Gen -1 Pharmacologymentioning

confidence: 97%

“…fluid and analgesic and did not require treatment with corticosteroids or cytokine antagonists, which remain the standard of care for cytokine release syndrome observed with some immunotherapy agents [48]. The reason that the hyperactivation of the immune system by some immunotherapy agents [48] has not been observed with GEN-1 is probably due to small changes in blood levels of immunocytokines. The effects of GEN-1 treatment on tumor Response Evaluation Criteria In Solid Tumors (RECIST) or patient survival have been encouraging, as described below, and warrant continued development of GEN-1 for the treatment of ovarian cancer.…”

Section: Gen -1 Pharmacologymentioning

confidence: 97%

GEN-1 Immunotherapy for the Treatment of Ovarian Cancer

et al. 2018

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GEN-1 is a gene-based immunotherapy, comprising a human IL-12 gene expression plasmid and a synthetic plasmid delivery system, delivered intraperitoneally (ip.) to produce local and persistent levels of a pleiotropic immunocytokine, IL-12, at the tumor site in patients with advanced ovarian cancer. The goal of local and persistent IL-12 delivery is to remodel the highly immunosuppressive tumor microenvironment to favor immune stimulation while avoiding serious systemic toxicities, a major limitation of recombinant IL-12 therapy. Safe and sustained local production of IL-12 and related immunocytokines at the tumor site could produce potentially more favorable immunological changes in the tumor microenvironment and antitumor responses than a bolus systemic delivery of recombinant IL-12. Treatment safety, clinical benefits and biological activity of GEN-1 ip. in patients with ovarian cancer and in representative animal models are described.

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New Immunotherapies in Oncology Treatment and Their Side Effect Profiles

Cited by 7 publications

References 54 publications

Acute cytokine release syndrome after a first dose of pembrolizumab as second-line treatment for metastatic, programmed death-ligand 1-positive, non-small-cell lung cancer

Acute cytokine release syndrome after a first dose of pembrolizumab as second-line treatment for metastatic, programmed death-ligand 1-positive, non-small-cell lung cancer

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab

GEN-1 Immunotherapy for the Treatment of Ovarian Cancer

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