Experience with ruxolitinib in the treatment of polycythaemia vera

Alimam, Samah; Harrison, Claire

doi:10.1177/2040620717693972

Cited by 11 publications

(5 citation statements)

References 58 publications

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“…Patients negative for HbsAg, anti-HBs, and anti-HBc should be considered for immunization [72]. Although recommended by some authors [73], there is no consensus in favor of routine testing for HCV and HIV before patients are started on ruxolitinib.…”

Section: Summary and Recommendations For Avoiding Complications From Ruxolitinib-associated Infections With A Special Focus On Polycythemmentioning

confidence: 99%

Ruxolitinib-Associated Infections in Polycythemia Vera: Review of the Literature, Clinical Significance, and Recommendations

Sadjadian

Wille

Grießhammer

2020

Cancers

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Ruxolitinib (RUX), a JAK1/JAK2 inhibitor, is approved for second-line therapy in patients with polycythemia vera (PV) who are resistant or intolerant to hydroxyurea. Due to the immunomodulatory and immunosuppressive effect of RUX, there is an increased susceptibility to infections. However, an increased risk of infection is inherent to even untreated myeloproliferative neoplasms (MPN). To obtain more information on the clinical significance of RUX-associated infections in PV, we reviewed the available literature. There is no evidence-based approach to managing infection risks. Most data on RUX-associated infections are available for MF. In all studies, the infection rates in the RUX and control groups were fairly similar, with the exception of infections with the varicella zoster virus (VZV). However, individual cases of bilateral toxoplasmosis retinitis, disseminated molluscum contagiosum, or a mycobacterium tuberculosis infection or a hepatitis B reactivation are reported. A careful assessment of the risk of infection for PV patients is required at the initial presentation and before the start of RUX. Screening for hepatitis B is recommended in all patients. The risk of RUX-associated infections is lower with PV than with MF, but compared to a normal population there is an increased risk of VZV infection. However, primary VZV prophylaxis for PV patients is not recommended, while secondary prophylaxis can be considered individually. As early treatment is most effective for VZV, patients should be properly informed and trained to seek medical advice immediately if cutaneous signs of VZV develop. Vaccination against influenza, herpes zoster, and pneumococci should be considered in all PV patients at risk of infection, especially if RUX treatment is planned. Current recommendations do not support adjusting or discontinuing JAK inhibition in MPN patients to reduce the risk of COVID-19.

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Section: Summary and Recommendations For Avoiding Complications From Ruxolitinib-associated Infections With A Special Focus On Polycythemmentioning

confidence: 99%

Ruxolitinib-Associated Infections in Polycythemia Vera: Review of the Literature, Clinical Significance, and Recommendations

Sadjadian

Wille

Grießhammer

2020

Cancers

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“…Nevertheless, no relationship between the etiopathogenesis of EM and headache have been described up to now in the literature. 72 , 73 …”

Section: Frequent Comorbiditiesmentioning

confidence: 99%

Erythromelalgia: a cutaneous manifestation of neuropathy?

Leroux¹

2018

An. Bras. Dermatol.

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The low prevalence of erythromelalgia, classified as an orphan disease, poses diagnostic and therapeutic difficulties. The aim of this review is to be an update of the specialized bibliography. Erythromelalgia is an infrequent episodic acrosyndrome affecting mainly both lower limbs symmetrically with the classic triad of erythema, warmth and burning pain. Primary erythromelalgia is an autosomal dominant inherited disorder, while secondary is associated with myeloproliferative diseases, among others. In its etiopathogenesis, there are neural and vascular abnormalities that can be combined. The diagnosis is based on exhaustive clinical history and physical examination. Complications are due to changes in the skin barrier function, ischemia and compromise of cutaneous nerves. Because of the complexity of its pathogenesis, erythromelalgia should always be included in the differential diagnosis of conditions that cause chronic pain and/or peripheral edema. The prevention of crisis is based on a strict control of triggers and promotion of preventive measures. Since there is no specific and effective treatment, control should focus on the underlying disease. However, there are numerous topical and systemic therapies that patients can benefit from.

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“…46,47 Reduction in JAK2 VAF may, from a conceptual standpoint, lead to improved clinical outcomes because a high JAK2 VAF indicates a greater risk of disease progression and thrombosis in patients with PV. 48,49 However, the clinical value of attaining a JAK2 VAF reduction and the association with risk of thrombosis and transformation have never been confirmed in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

The MDM2 antagonist idasanutlin in patients with polycythemia vera: results from a single-arm phase 2 study

et al. 2022

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Idasanutlin, an MDM2 antagonist, showed clinical activity and rapid reduction in JAK2 V617F allele burden in patients with polycythemia vera (PV) in a phase 1 study. This open-label, phase 2 study evaluated idasanutlin in patients with hydroxyurea (HU)-resistant/intolerant PV, per the European LeukemiaNet criteria, and phlebotomy dependence; prior ruxolitinib exposure was permitted. Idasanutlin was administered once daily, days 1-5 of each 28-day cycle. The primary endpoint was composite response (hematocrit control and spleen volume reduction >35%) in patients with splenomegaly, and hematocrit control in patients without splenomegaly at week 32. Key secondary endpoints included safety, complete hematologic response (CHR), patient-reported outcomes, and molecular responses. All patients (n=27) received idasanutlin; 16 had response assessment (week 32). Among responders with baseline splenomegaly (n=13), 9 (69%) attained any spleen volume reduction and 1 achieved composite response. Nine patients (56%) achieved hematocrit control, and 8 patients (50%) achieved CHR. Overall, 43% of evaluable patients (n=6/14) showed a ≥50% reduction in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (week 32). Nausea (93%), diarrhea (78%), and vomiting (41%) were the most common adverse events, with grade ≥3 nausea and vomiting experienced in 3 patients (11%) and 1 patient (4%), respectively. Reduced JAK2 V617F allele burden occurred early (after 3 cycles), with a median reduction of 76%, and associated with achieving CHR and hematocrit control. Overall, the idasanutlin dosing regimen showed clinical activity and rapidly reduced JAK2 allele burden in patients with HU-resistant/intolerant PV but was associated with low-grade gastrointestinal toxicity, leading to poor long-term tolerability. Registration: NCT03287245.

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Experience with ruxolitinib in the treatment of polycythaemia vera

Cited by 11 publications

References 58 publications

Ruxolitinib-Associated Infections in Polycythemia Vera: Review of the Literature, Clinical Significance, and Recommendations

Ruxolitinib-Associated Infections in Polycythemia Vera: Review of the Literature, Clinical Significance, and Recommendations

Erythromelalgia: a cutaneous manifestation of neuropathy?

The MDM2 antagonist idasanutlin in patients with polycythemia vera: results from a single-arm phase 2 study

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