St James's Institute of Oncology, St James's University Hospital, Leeds, UK.
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
Br J Haematol. 2022 Dec;199(5):707-719. doi: 10.1111/bjh.18427. Epub 2022 Aug 26.
The GA101 (obinutuzumab) monocLonal Antibody as Consolidation Therapy In chronic lymphocytic leukaemia (CLL) (GALACTIC) was a seamless phase II/III trial designed to test whether consolidation with obinutuzumab is safe and eradicates minimal residual disease (MRD) and, subsequently, whether this leads to prolonged progression-free survival (PFS) in patients with CLL who have recently responded to chemo-immunotherapy. Patients with a response 3-24 months after chemotherapy were assessed for MRD. MRD-positive patients were randomised to receive consolidation therapy with obinutuzumab or no consolidation. The trial closed after the phase II part due to slow recruitment. In all, 48 patients enrolled of whom 19 were MRD negative and were monitored. Of the 29 MRD-positive patients, 14 were randomised to receive consolidation and 15 to no consolidation. At 6 months after randomisation, 10 and 13 consolidated patients achieved MRD negativity by flow cytometry (sensitivity 10 ) in bone marrow and peripheral blood respectively. PFS was significantly better in consolidated patients compared to non-consolidated patients (p = 0.001). No difference was observed in PFS, overall survival or duration of MRD negativity when comparing the 10 MRD-negative patients after consolidation with the 19 MRD-negative patients in the monitoring group. Common adverse events in the consolidation arm were thrombocytopenia, infection, and cough. Only 1% of events were infusion-related reactions. This observation provides further evidence that consolidation to achieve MRD negativity improves outcomes in CLL and that obinutuzumab is well tolerated in patients with low levels of disease.
GA101（奥滨尤妥珠单抗）单克隆抗体作为慢性淋巴细胞白血病（CLL）的巩固治疗（GALACTIC）是一项无缝的 II/III 期试验，旨在测试奥滨尤妥珠单抗巩固治疗是否安全，是否能消除微小残留病（MRD），进而是否能延长近期接受化疗免疫治疗后缓解的 CLL 患者的无进展生存期（PFS）。化疗后 3-24 个月有缓解的患者评估 MRD。MRD 阳性的患者被随机分为接受奥滨尤妥珠单抗巩固治疗或不接受巩固治疗。由于招募速度缓慢，该试验在 II 期部分结束后关闭。共纳入 48 例患者，其中 19 例 MRD 阴性并进行监测。29 例 MRD 阳性患者中，14 例随机接受巩固治疗，15 例未接受巩固治疗。在随机分组后 6 个月时，10 例和 13 例接受巩固治疗的患者在骨髓和外周血中通过流式细胞术分别达到了 10 的 MRD 阴性（敏感性 10 ）。与未接受巩固治疗的患者相比，接受巩固治疗的患者 PFS 显著更好（p = 0.001）。在比较 10 例巩固治疗后 MRD 阴性的患者与监测组中 19 例 MRD 阴性的患者的 PFS、总生存期或 MRD 阴性持续时间时，未观察到差异。巩固治疗组的常见不良事件包括血小板减少、感染和咳嗽。仅有 1%的事件为输液相关反应。这一观察结果进一步表明，达到 MRD 阴性的巩固治疗可改善 CLL 的预后，并且奥滨尤妥珠单抗在疾病程度较低的患者中具有良好的耐受性。
