A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma.
Haematologica
; 103(5): 840-848, 2018 05.
Article
en En
| MEDLINE
| ID: mdl-29351986
ABSTRACT
JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in Hodgkin lymphoma. In this phase II study we assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in patients with relapsed/refractory Hodgkin lymphoma. The primary objective was overall response rate according to the International Harmonization Project 2007 criteria. Thirty-three patients with advanced disease (median number of prior lines of treatment 5; refractory 82%) were included; nine (27.3%) received at least six cycles of ruxolitinib and six (18.2%) received more than six cycles. The overall response rate after six cycles was 9.4% (3/32 patients). All three responders had partial responses; another 11 patients had transient stable disease. Best overall response rate was 18.8% (6/32 patients). Rapid alleviation of B-symptoms was common. The median duration of response was 7.7 months, median progression-free survival 3.5 months (95% CI 1.9-4.6), and the median overall survival 27.1 months (95% CI 14.4-27.1). Forty adverse events were reported in 14/33 patients (42.4%). One event led to treatment discontinuation, while 87.5% of patients recovered without sequelae. Twenty-five adverse events were grade 3 or higher. These events were mostly anemia (n=11), all considered related to ruxolitinib. Other main causes of grade 3 or higher adverse events included lymphopenia and infections. Of note, no cases of grade 4 neutropenia or thrombocytopenia were observed. Ruxolitinib shows signs of activity, albeit short-lived, beyond a simple anti-inflammatory effect. Its limited toxicity suggests that it has the potential to be combined with other therapeutic modalities. ClinicalTrials.gov NCT01877005.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Pirazoles
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Enfermedad de Hodgkin
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Terapia Recuperativa
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Resistencia a Antineoplásicos
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Janus Quinasa 1
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Janus Quinasa 2
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Recurrencia Local de Neoplasia
Tipo de estudio:
Clinical_trials
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Observational_studies
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Prognostic_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Haematologica
Año:
2018
Tipo del documento:
Article
País de afiliación:
Bélgica