HPV-related papillary squamous cell carcinoma of the tonsil during treatment with fingolimod

Benedetti, Maria Donata; Marangi, Antonio; Bozzetti, Silvia; Gobbin, Francesca; Turatti, Marco; Pea, Maurizio; Gajofatto, Alberto; Mocella, Stelio

doi:10.1016/j.msard.2018.04.018

Cited by 21 publications

(16 citation statements)

References 4 publications

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“…All three drugs are known to decrease blood lymphocyte counts, but importantly this effect does not reflect the death or loss of lymphocytes, especially not those in the bone marrow -it means that these cells might still be recruitable and functional but entrapped. Fingolimod treatment has been associated with increased rates of varicella zoster virus (VZV) activation or reactivation 74 , and other viral infections, such as PML, have been described in rare cases [75][76][77] . Siponimod and ozanimod are more selective for the S1PR than is fingolimod but they have similar effects on lymphocyte counts and have been associated with similar infections [78][79][80][81] .…”

Section: Fingolimod Siponimod and Ozanimodmentioning

confidence: 99%

Neurological immunotherapy in the era of COVID-19 — looking for consensus in the literature

Korsukewitz¹,

Reddel

Bar‐Or

et al. 2020

Nat Rev Neurol

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Section: Fingolimod Siponimod and Ozanimodmentioning

confidence: 99%

Neurological immunotherapy in the era of COVID-19 — looking for consensus in the literature

Korsukewitz¹,

Reddel

Bar‐Or

et al. 2020

Nat Rev Neurol

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“…Other concerns related to S1PR agonist/modulators are leukopenia (reversible with drug discontinuation), teratogenicity, pulmonary disorders, transaminase elevation, anemia, macular edema, headache, and human papillomavirus infections [ 12 , 58 , 113 , 114 ].…”

Section: Safety and Adverse Eventsmentioning

confidence: 99%

Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis

Pérez-Jeldres

Álvarez-Lobos

Rivera–Nieves

2021

Drugs

126

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Sphingosine-1-phosphate (S1P) is a bioactive lipid metabolite that exerts its actions by engaging 5 G-protein-coupled receptors (S1PR1-S1PR5). S1P receptors are involved in several cellular and physiological events, including lymphocyte/hematopoietic cell trafficking. An S1P gradient (low in tissues, high in blood), maintained by synthetic and degradative enzymes, regulates lymphocyte trafficking. Because lymphocytes live long (which is critical for adaptive immunity) and recirculate thousands of times, the S1P-S1PR pathway is involved in the pathogenesis of immune-mediated diseases. The S1PR1 modulators lead to receptor internalization, subsequent ubiquitination, and proteasome degradation, which renders lymphocytes incapable of following the S1P gradient and prevents their access to inflammation sites. These drugs might also block lymphocyte egress from lymph nodes by inhibiting transendothelial migration. Targeting S1PRs as a therapeutic strategy was first employed for multiple sclerosis (MS), and four S1P modulators (fingolimod, siponimod, ozanimod, and ponesimod) are currently approved for its treatment. New S1PR modulators are under clinical development for MS, and their uses are being evaluated to treat other immune-mediated diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis. A clinical trial in patients with COVID-19 treated with ozanimod is ongoing. Ozanimod and etrasimod have shown promising results in IBD; while in phase 2 clinical trials, ponesimod has shown improvement in 77% of the patients with psoriasis. Cenerimod and amiselimod have been tested in SLE patients. Fingolimod, etrasimod, and IMMH001 have shown efficacy in RA preclinical studies. Concerns relating to S1PR modulators are leukopenia, anemia, transaminase elevation, macular edema, teratogenicity, pulmonary disorders, infections, and cardiovascular events. Furthermore, S1PR modulators exhibit different pharmacokinetics; a well-established first-dose event associated with S1PR modulators can be mitigated by gradual up-titration. In conclusion, S1P modulators represent a novel and promising therapeutic strategy for immune-mediated diseases.

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“…Annual HPV screening is only recommended in alemtuzumab-treated MS patients, a similar approach to recommended screening in HIV patients. HPV-related benign lesions and cancers are increasingly reported in fingolimod-treated patients, suggesting an increased incidence of skin and mucosal warts with fingolimod [ 54 , 55 ], the majority being HPV-related cervical dysplasia in female patients and one unique case of HPV-related papillary squamous cell carcinoma of the tonsil in male patient [ 56 ]. Screening for HPV and cervical cancer is not typically performed as part as routine testing for patient on fingolimod.…”

Section: Monitoring Of Adverse Eventsmentioning

confidence: 99%

Safety of Newer Disease Modifying Therapies in Multiple Sclerosis

et al. 2020

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In the past decade, the therapeutic arsenal for multiple sclerosis has expanded greatly. Newer more potent disease modifying therapies (DMTs) with varying mechanisms of actions are increasingly used early in the disease course. These newer DMTs include oral therapies (teriflunomide, dimethyl fumarate, fingolimod, siponimod, ozanimod, and cladribine) and infusion therapies (natalizumab, alemtuzumab, and ocrelizumab), and are associated with better control of disease activity and long-term outcomes in patients with MS compared to older injectable therapies (interferon beta and glatiramer acetate). However, they are associated with safety concerns and subsequent monitoring requirements. Adverse events are initially observed in phase 2 and 3 clinical trials, and further long-term data are collected in phase 3 extension studies, case series, and post-marketing reports, which highlight the need to periodically re-evaluate and adjust monitoring strategies to optimize treatment safety in an individualized approach.

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HPV-related papillary squamous cell carcinoma of the tonsil during treatment with fingolimod

Cited by 21 publications

References 4 publications

Neurological immunotherapy in the era of COVID-19 — looking for consensus in the literature

Neurological immunotherapy in the era of COVID-19 — looking for consensus in the literature

Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis

Safety of Newer Disease Modifying Therapies in Multiple Sclerosis

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