Ruxolitinib for treatment of refractory hemophagocytic lymphohistiocytosis

Broglie, Larisa; Pommert, Lauren; Rao, Sridhar; Thakar, Monica S.; Phelan, Rachel; Margolis, David; Talano, Julie

doi:10.1182/bloodadvances.2017007526

Cited by 114 publications

(83 citation statements)

References 23 publications

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“…When macrophages are activated by a stimulus such as infection there is interaction with, and regulation by, natural killer (NK) or cytotoxic lymphocytes Previously, there have been case reports of ruxolitinib use in HLH after failure of established therapies, primarily dexamethasone, and etoposide. 4,5 Clearly, use of cytotoxic agents in critically ill patients with secondary HLH can be fraught with challenges and at times may not be feasible. Our group first reported first-line use of ruxolitinib in a patient with secondary HLH from disseminated histoplasmosis.…”

Section: Ruxolitinib As First-line Treatment In Secondary Hemophagocymentioning

confidence: 99%

“…We conducted a post hoc evaluation of data from the phase 3 DACO-016 study (NCT00260832) comparing decitabine versus treatment choice (TC) in patients aged 65 years with newly diagnosed, de novo or secondary AML (20% blasts), and poor/intermediate-risk cytogenetics (Southwest Oncology Group [SWOG] categorization). 4 Patients were randomized 1:1 to decitabine (20 mg/m 2 /day for five consecutive days every 4 weeks) or TC (best supportive care or cytarabine 20 mg/m 2 /day for 10 days every 4 weeks).…”

Section: Supporting Informationmentioning

confidence: 99%

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Ruxolitinib as first‐line treatment in secondary hemophagocytic lymphohistiocytosis: A second experience

et al. 2018

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Section: Ruxolitinib As First-line Treatment In Secondary Hemophagocymentioning

confidence: 99%

Section: Supporting Informationmentioning

confidence: 99%

Ruxolitinib as first‐line treatment in secondary hemophagocytic lymphohistiocytosis: A second experience

et al. 2018

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“…Under the rationale that 9p24.1 amplification is not only linked to PD-L1 expression, but also to JAK2 activation, we used ruxolitinib for both HLH and GZL treatment, and repeatedly observed transient disease stabilization. 17,18 However, owing to the combination of multiple drugs, the contribution of single agents to transient disease stabilization in this setting remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Management of children and adolescents with gray zone lymphoma: A case series

Perwein

Lackner

Ebetsberger‐Dachs

et al. 2020

Pediatric Blood & Cancer

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Background Data on management of gray zone lymphoma (GZL) in children and adolescents are scarce. Procedure This retrospective study assessed clinical characteristics and outcome in six Austrian patients with GZL less than 18 years of age (male‐to‐female ratio: 1:1; median age: 15.8 years). Results Two patients each had a classical Hodgkin lymphoma (cHL)‐like and composite GZL subtype, and one patient each had a large B‐cell non‐Hodgkin lymphoma (LBCL)‐like and sequential GZL subtype. All had advanced disease with mediastinal and extranodal involvement. Five patients received an LBCL‐ and one patient a cHL‐directed polychemotherapy ± radiotherapy. Out of the former patients, three survived, including two who relapsed and underwent high‐dose chemotherapy with autologous stem cell rescue. The latter patient survived. Conclusions GZL remains a diagnostic and therapeutic challenge, necessitating the development of novel treatment concepts performed in a prospective setting.

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“…70 Ruxolitinib has also been effective in a number of case reports of patients with refractory HLH. 71,72 As ruxolitinib can inhibit T-cell proliferation, it is plausible it might impact the efficacy of CAR-T.…”

Section: Y Tokine Rele a S E Syndromementioning

confidence: 99%

Cellular therapy: Immune‐related complications

Oved

Barrett

Teachey

2019

Immunological Reviews

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The advent of chimeric antigen receptor T (CAR‐T) and the burgeoning field of cellular therapy has revolutionized the treatment of relapsed/refractory leukemia and lymphoma. This personalized “living therapy” is highly effective against a number of malignancies, but this efficacy is tempered by side effects relatively unique to immunotherapies, including CAR‐T. The overwhelming release of cytokines and chemokines by activated CAR‐T and other secondarily activated immune effector cells can lead to cytokine release syndrome (CRS), which can have clinical and pathophysiology similarities to systemic inflammatory response syndrome and macrophage activating syndrome/hemophagocytic lymphohistiocytosis. Tocilizumab, an anti‐IL6 receptor antibody, was recently FDA approved for treatment of CRS after CAR‐T based on its ability to mitigate CRS in many patients. Unfortunately, some patients are refractory and additional therapies are needed. Patients treated with CAR‐T can also develop neurotoxicity and, as the biology is poorly understood, current therapeutic interventions are limited to supportive care. Nevertheless, a number of recent studies have shed new light on the pathophysiology of CAR‐T‐related neurotoxicity, which will hopefully lead to effective treatments. In this review we discuss some of the mechanistic contributions intrinsic to the CAR‐T construct, the tumor being treated, and the individual patient that impact the development and severity of CRS and neurotoxicity. As CAR‐T and cellular therapy have redefined the concept of personalized medicine, so too will personalization be necessary in managing the unique side effects of these therapies.

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Ruxolitinib for treatment of refractory hemophagocytic lymphohistiocytosis

Abstract: Key Points Optimal salvage therapy for refractory HLH is unknown. In our patient, ruxolitinib treatment led to clinical remission of refractory HLH.

Cited by 114 publications

References 23 publications

Ruxolitinib as first‐line treatment in secondary hemophagocytic lymphohistiocytosis: A second experience

Ruxolitinib as first‐line treatment in secondary hemophagocytic lymphohistiocytosis: A second experience

Management of children and adolescents with gray zone lymphoma: A case series

Cellular therapy: Immune‐related complications

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