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Ruxolitinib for pediatric patients with treatment-naïve and steroid-refractory acute graft-versus-host disease (REACH4).
Locatelli, Franco; Kang, Hyoung Jin; Bruno, Benedicte; Gandemer, Virginie; Rialland-Battisti, Fanny; Faraci, Maura; Takahashi, Yoshiyuki; Koh, Katsuyoshi; Bittencourt, Henrique; Cleary, Grace; Rosko, Christine; Li, Xuechan; St Pierre, Annie; Prahallad, Anirudh Cadapa; Diaz-de-Heredia, Christina.
Afiliação
  • Locatelli F; Ospedale Bambino Gesù, Rome, Italy.
  • Kang HJ; Seoul National University College of Medicine, Seoul, Korea, Republic of.
  • Bruno B; chu lille hématologie pédiatrique, lille, France.
  • Gandemer V; University Hospital of Rennes, Rennes, France.
  • Rialland-Battisti F; HME, CHU Nantes, Nantes, France.
  • Faraci M; IRCCS Istituto Giannina Gaslini, Genova, Italy.
  • Takahashi Y; Nagoya University Graduate School of medicine, Nagoya, Japan.
  • Koh K; Saitama Children's Medical Center, Saitama, Japan.
  • Bittencourt H; CHU Sainte-Justine, Montreal, Canada.
  • Cleary G; Novartis Ireland Limited, Dublin, Ireland.
  • Rosko C; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States.
  • Li X; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States.
  • St Pierre A; Novartis Institute for Biomedical Research (NIBR), Basel, Switzerland.
  • Prahallad AC; Novartis Pharma AG, Basel, Switzerland.
  • Diaz-de-Heredia C; Hospital Universitari Vall d'Hebron and Vall d'Hebron Institute of Research, Barcelona, Spain.
Blood ; 2024 Jul 24.
Article em En | MEDLINE | ID: mdl-39046767
ABSTRACT
In REACH4 (NCT03491215), a phase 1/2, open-label, single-arm, multicenter study, the pharmacokinetics (PK), efficacy, and safety of ruxolitinib were evaluated in treatment-naïve and steroid-refractory pediatric patients with grade II-IV acute graft-versus-host disease (aGVHD; n=45). Ruxolitinib dosing was based on age and targeted the exposure in adults receiving 10 mg twice daily; group 1 (≥12 to <18 years) received 10 mg twice daily and preliminary starting doses for groups 2 (≥6 to <12 years) and 3 (≥2 to <6 years) were 5 mg twice daily and 4 mg/m2 twice daily, respectively. Phase 1 primary objective was to assess ruxolitinib PK parameters and define an age-appropriate recommended phase 2 dose (RP2D) for patients <12 years of age. Phase 2 primary objective was to measure the activity of ruxolitinib as assessed by overall response rate (ORR) at day 28; the key secondary objective was to assess the durable ORR at day 56. Ruxolitinib exposure was comparable across age groups; starting doses were confirmed as the RP2D. The median duration of ruxolitinib exposure was 3.8 months (range 0.3-11.2). ORR in all patients was 84.4% (90% confidence interval [CI], 72.8-92.5) at day 28, with a durable ORR at day 56 of 66.7% (90% CI, 53.4-78.2); high response rates were observed across age groups and in both treatment-naïve and steroid-refractory subgroups. Adverse events were consistent with those expected in ruxolitinib-treated patients with aGvHD (anemia, decreased neutrophil and leukocyte count). In pediatric patients with aGvHD, ruxolitinib showed clinically meaningful efficacy with no new safety signals.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Blood Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Blood Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Itália