Medical Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland.
Oncology and Hematology, Kantonsspital Graubuenden, Chur, Switzerland.
Blood Adv. 2022 Jul 12;6(13):3911-3920. doi: 10.1182/bloodadvances.2021006520.
This phase 1 study evaluated safety, tolerability, and preliminary efficacy of obinutuzumab in combination with venetoclax in patients with previously untreated grade 1-3a follicular lymphoma in need of systemic therapy. Two DLs of venetoclax were evaluated with an expansion cohort at the recommended phase 2 dose. Twenty-five patients were enrolled. The recommended phase 2 dose was venetoclax 800 mg OD continuously for 6 cycles starting on day 2 of cycle 1, with obinutuzumab 1000 mg on days 1, 8, and 15 of cycle 1 and on day 1 of cycles 2 to 6, followed by obinutuzumab maintenance every 2 months for 2 years. Only 1 patient had a DLT consisting of grade 4 thrombocytopenia after the first obinutuzumab infusion. Neutropenia was the most common adverse event of grade ≥3 at least possibly attributed to study treatment. Twenty-four patients were evaluable for response after cycle 6 by computed tomography (CT) and 19 by positron emission tomography/CT (PET/CT): overall and complete response rates were 87.5% (95% CI, 67.6% to 97.3%) and 25% (95% CI, 9.8% to 46.7%) in the CT-evaluated patients and 84.2% (95% CI, 60.4% to 96.6%) and 68.4% (95% CI, 43.4% to 87.4%), respectively, in the PET/CT-evaluated patients. One-year progression-free survival was 77.8% (95% CI, 54.6% to 90.1%) and 79% (95% CI, 47.9% to 92.7%) for CT and PET/CT-evaluable patients, respectively, whereas progression-free survival at 30 months was 73.2% (95% CI, 49.8%, 87.0%) as assessed by CT and 79.0% (95% CI, 47.9%, 92.7%) by PET/CT. Despite the activity observed, our results do not support further development of the combination in this patient population. This trial was registered at www.clinicaltrials.gov as #NCT02877550.
这项 1 期研究评估了奥滨尤妥珠单抗联合 Venetoclax 在初治 1-3a 级滤泡淋巴瘤患者中的安全性、耐受性和初步疗效，这些患者需要系统治疗。评价了 Venetoclax 的两个 DL，扩展队列的推荐 2 期剂量。共入组 25 例患者。推荐的 2 期剂量为 Venetoclax 800mg 每日一次，连续 6 个周期，第 1 周期第 2 天开始，第 1 周期第 1、8 和 15 天以及第 2 至 6 周期第 1 天给予奥滨尤妥珠单抗，随后每 2 个月给予奥滨尤妥珠单抗维持治疗 2 年。只有 1 例患者在首次奥滨尤妥珠单抗输注后出现剂量限制性毒性，为 4 级血小板减少症。至少可能与研究治疗相关的中性粒细胞减少症是最常见的≥3 级不良事件。24 例患者在第 6 周期后通过计算机断层扫描（CT）评估、19 例患者通过正电子发射断层扫描/CT（PET/CT）评估有反应：在 CT 可评估患者中，总缓解率和完全缓解率分别为 87.5%（95%CI，67.6%至 97.3%）和 25%（95%CI，9.8%至 46.7%），在 PET/CT 可评估患者中，分别为 84.2%（95%CI，60.4%至 96.6%）和 68.4%（95%CI，43.4%至 87.4%）。1 年无进展生存分别为 CT 和 PET/CT 可评估患者的 77.8%（95%CI，54.6%至 90.1%）和 79%（95%CI，47.9%至 92.7%），30 个月时的无进展生存分别为 CT 评估的 73.2%（95%CI，49.8%，87.0%）和 PET/CT 评估的 79.0%（95%CI，47.9%，92.7%）。尽管观察到了活性，但我们的结果不支持在该患者人群中进一步开发该联合用药。该试验在 www.clinicaltrials.gov 上注册，编号为 #NCT02877550。
