Phase I / II study of brentuximab vedotin in Japanese patients with relapsed or refractory CD30‐positive Hodgkin's lymphoma or systemic anaplastic large‐cell lymphoma

Abstract

Brentuximab vedotin is an antibody–drug conjugate that selectively delivers the antimicrotubule agent monomethyl auristatin E into CD30-expressing cells. To assess its safety, pharmacokinetics, and efficacy in Japanese patients with refractory or relapsed CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma, we carried out a phase I/II study. Brentuximab vedotin was given i.v. on day 1 of each 21-day cycle up to 16 cycles. In the phase I part of a dose-escalation design, three patients per cohort were treated at doses of 1.2 and 1.8 mg/kg. In the phase II part, a dose of 1.8 mg/kg was given to 14 patients (nine with Hodgkin's lymphoma and five with systemic anaplastic large-cell lymphoma). The median number of treatment cycles was 16 (range, 4–16). In the phase I part, no dose-limiting toxicity event was observed. In the total population, common adverse events included lymphopenia (80%), neutropenia (65%), leukopenia (65%), and peripheral sensory neuropathy (60%). Grade 3/4 adverse events in more than two patients were lymphopenia (50%) and neutropenia (15%). The pharmacokinetic profile was similar to that observed in the previous studies in the USA. In the phase II part, six patients (67%) with Hodgkin's lymphoma achieved an objective response with 56% of complete response rate, and five patients (100%) with systemic anaplastic large-cell lymphoma achieved an objective response with 80% of complete response rate. These results show that brentuximab vedotin has an acceptable safety profile and promising antitumor activity in the Japanese population. This trial was registered in JAPIC Clinical Trials Information (JapicCTI-111650).This phase I/II study was to investigate the tolerability, safety and efficacy of brentuximab vedotin. This study indicates that 1.8 mg/kg brentuximab vedotin given every 3 weeks has a manageable safety profile and has high overall tumor response rate in Japanese patients with relapsed or refractory Hodgkin lymphoma or systemic anaplastic large-cell lymphoma.

Anaplastic large cell lymphoma: pathology, genetics, and clinical aspects

“…In Japan, a phase 1/2 study was performed, and similar results were obtained. 191 Retreatment with BV for relapsed CD30+ lymphomas (21 Hodgkin lymphoma and eight ALCL) has been evaluated in a phase II study, and the ORR in patients with ALCL was 88%. 192 BV was also tested in the initial treatment of ALCL.…”

Targeted Drug Brentuximab Vedotin for Treatment of Relapsed or Refractory Cd30-Positive Hodgkin’s Lymphoma

“…Они были полу-чены из исследований I фазы SGN35-0001 [28], SGN35-0002 [29], японского исследования TB-BC010088 [30] и программы дорегистрационного использования препа-рата по запросу врача (Named Patient Program, NPP).…”

“…Исследования по отдельности не были включены в об-зор, так как все они содержат менее 20 пациентов с ЛХ, получивших БВ в дозе 1,8 мг / кг (в японском исследова-нии -12 пациентов [30], в исследовании SGN35-0001 c эскалацией дозы -12 пациентов [28], в исследовании SGN35-0002 -0 пациентов [29]). …”

Non-Hodgkin’s Lymphomas in Children: 25-Year Clinical Experience

“…Экспрессируемый на клетках АККЛ CD30 стал мишенью для химерного моноклонального анти-CD30-антитела, конъюгированного с синтетическим микроту-булярным монометилауристатином Е, -брентуксимаба ведотина, который используется в лечении АККЛ [64].…”