Reactivation of herpes simplex virus infection in a patient undergoing ruxolitinib treatment

Tong, Lana X.; Jackson, Julie; Kerstetter, Justin; Worswick, Scott

doi:10.1016/j.jaad.2013.09.035

Cited by 42 publications

(21 citation statements)

References 5 publications

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“…Intriguingly, ruxolitinib therapy is also associated with severe infections, among which disseminated tuberculosis (7,8), reactivation of hepatitis B (9), progressive multifocal leukencephalopathy (10), toxoplasmosis retinitis (11), and Epstein-Barr virus-associated aggressive lymphoma (J. Richter, Lund University, Lund, Sweden; personal communication, June 2014) are the most alarming ones. Moreover, reactivation of herpes simplex and varicella zoster infections in ruxolitinib-treated patients is frequent, similar to patients with an inherited functional NK cell deficiency (49).…”

Section: Discussionmentioning

confidence: 96%

JAK Inhibition Impairs NK Cell Function in Myeloproliferative Neoplasms

et al. 2015

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Ruxolitinib is a small-molecule inhibitor of the JAK kinases, which has been approved for the treatment of myelofibrosis, a rare myeloproliferative neoplasm (MPN), but clinical trials are also being conducted in inflammatory-driven solid tumors. Increased infection rates have been reported in ruxolitinib-treated patients, and natural killer (NK) cells are immune effector cells known to eliminate both virus-infected and malignant cells. On this basis, we sought to compare the effects of JAK inhibition on human NK cells in a cohort of 28 MPN patients with or without ruxolitinib treatment and 24 healthy individuals. NK cell analyses included cell frequency, receptor expression, proliferation, immune synapse formation, and cytokine signaling. We found a reduction in NK cell numbers in ruxolitinib-treated patients that was linked to the appearance of clinically relevant infections. This reduction was likely due to impaired maturation of NK cells, as reflected by an increased ratio in immature to mature NK cells. Notably, the endogenous functional defect of NK cells in MPN was further aggravated by ruxolitinib treatment. In vitro data paralleled these in vivo results, showing a reduction in cytokine-induced NK cell activation. Further, reduced killing activity was associated with an impaired capacity to form lytic synapses with NK target cells. Taken together, our findings offer compelling evidence that ruxolitinib impairs NK cell function in MPN patients, offering an explanation for increased infection rates and possible longterm side effects associated with ruxolitinib treatment. Cancer Res; 75(11);

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Section: Discussionmentioning

confidence: 96%

JAK Inhibition Impairs NK Cell Function in Myeloproliferative Neoplasms

et al. 2015

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“…To our knowledge, only one case of pulmonary cryptococcosis in a ruxolitinib-treated patient has been reported previously [9], making this the second report of pulmonary cryptococcosis in a ruxolitinib-treated patient. Tuberculosis [4], [11], herpes zoster virus infection [3], [6], herpes simplex virus infection [12], toxoplasmosis retinitis [13], and cryptococcal meningoencephalitis [14] have occurred in patients treated with ruxolitinib. Infections such as tuberculosis, viral infections, and fungal infections are mainly controlled by cell-mediated immunity.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary cryptococcosis in a ruxolitinib-treated patient with primary myelofibrosis

Hirano

Yamasaki

Saito

et al. 2017

Respiratory Medicine Case Reports

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We present the case of a 79-year-old man who showed multiple pulmonary nodules on chest computed tomography (CT) after being treated for 6 months with ruxolitinib, an inhibitor of Janus kinase (JAK) 1 and 2, to treat primary myelofibrosis. We examined the lesions by bronchoscopy, and the biopsy specimen revealed fungus bodies of Cryptococcus with granulomatous inflammation. As a result, the patient was diagnosed with pulmonary cryptococcosis. The patient was treated with fluconazole (200 mg daily for 2 weeks) with concomitant ruxolitinib administration, but the pulmonary lesions progressed. Subsequently, the patient was treated with voriconazole (300 mg daily for 3 weeks), but the lesions worsened further. The administration of ruxolitinib was therefore discontinued, and the dosage of voriconazole was increased to 400 mg daily. Three months later, the pulmonary lesions diminished in size. The present case of pulmonary cryptococcosis occurred in a patient treated with ruxolitinib. Treatment of pulmonary cryptococcosis with concomitant JAK inhibitor administration may result in poor treatment efficacy. It might be better to stop administration of JAK inhibitors, if possible, in patients being treated for pulmonary cryptococcosis.

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“…Although such effects may have played a role in isolated cases of serious opportunistic infections in patients on ruxolitinib therapy, including progressive multifocal leukoencephalopathy (PML) [84], reactivation of hepatitis B virus [85], pneumonia [86], disseminated tuberculosis [87], reactivation of herpes simplex virus [88] and Pneumocystis jiroveci pneumonitis [89], the relationship of these infections with ruxolitinib treatment remains unclear. Common infections that occurred during randomized treatment in patients in the ruxolitinib arm of COMFORT-I were urinary tract infections and herpes zoster (Table 6) [32].…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Efficacy and safety of ruxolitinib in the treatment of patients with myelofibrosis

Tam

Verstovšek

2015

Future Oncol.

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The JAK 1 and JAK2 inhibitor ruxolitinib has approved indications in myelofibrosis, a BCR-ABL1-negative myeloproliferative neoplasm associated with progressive bone marrow fibrosis and shortened survival. In Phase III clinical studies, ruxolitinib provided rapid and durable improvement of myelofibrosis-related splenomegaly and symptoms irrespective of mutation status, and was associated with a survival advantage compared with placebo or best available therapy. Because of dose-dependent cytopenias, blood count monitoring and dose titration are important to optimize therapy. Specific precautions apply to the treatment of patients with or at risk of serious infections. Discontinuation of ruxolitinib generally leads to symptom return within 1 week. Ruxolitinib also is approved for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

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Reactivation of herpes simplex virus infection in a patient undergoing ruxolitinib treatment

Cited by 42 publications

References 5 publications

JAK Inhibition Impairs NK Cell Function in Myeloproliferative Neoplasms

JAK Inhibition Impairs NK Cell Function in Myeloproliferative Neoplasms

Pulmonary cryptococcosis in a ruxolitinib-treated patient with primary myelofibrosis

Efficacy and safety of ruxolitinib in the treatment of patients with myelofibrosis

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