Meyer Cancer Center, Weill Medical College of Cornell University and New York-Presbyterian Hospital, New York, NY, USA.
MD Anderson Cancer Center, Houston, TX, USA.
Br J Haematol. 2019 Apr;185(1):53-64. doi: 10.1111/bjh.15768. Epub 2019 Feb 5.
Rituximab monotherapy has proven efficacy in treatment-naïve, asymptomatic advanced-stage follicular lymphoma (FL). Ofatumumab is a fully humanized anti-CD20 monoclonal antibody with increased CD20 affinity and complement-dependent cytotoxicity. This phase 2 trial (NCT01190449) evaluated ofatumumab in patients with untreated, low/intermediate-risk FL International Prognostic Index (FLIPI), advanced-stage FL to determine single-agent efficacy. Patients with measurable disease in stages III/IV or bulky stage II, regardless of Groupe d'Etude des Lymphomes Folliculaires criteria, received 4 weekly 1000 mg doses followed by four extended induction doses once every 8 weeks. Primary endpoint was overall response rate (ORR) to 1000 mg; secondary endpoints were progression-free survival (PFS) and safety. Fifty-one patients were enrolled. Fifteen patients were randomized to 500 mg prior to discontinuing that arm for slow accrual. Among 36 patients on the 1000 mg arm, ORR was 84%, median PFS was 1·9 years and median response duration was 23·7 months. All patients remain alive. No grade 4 infusion reactions or grade 3/4 infections occurred. Grade 3 infusion reactions occurred in 25% in the 1000 mg arm only (all first infusion); all but two patients continued on study. Discontinuation was 6% for the total study population. Ofatumumab monotherapy administered by extended induction in untreated, low/intermediate-risk FLIPI, advanced-stage FL is well tolerated and active. Activity appears similar to that reported with single-agent rituximab.
利妥昔单抗单药治疗在未经治疗、无症状的晚期滤泡性淋巴瘤(FL)患者中已被证实具有疗效。奥法妥珠单抗是一种完全人源化的抗 CD20 单克隆抗体,具有更高的 CD20 亲和力和补体依赖性细胞毒性。这项 2 期临床试验(NCT01190449)评估了奥法妥珠单抗在未经治疗的低/中危滤泡性淋巴瘤国际预后指数(FLIPI)、晚期 FL 患者中的疗效,以确定单药疗效。有可测量疾病的 III/IV 期或大块的 II 期患者,无论是否符合滤泡淋巴瘤研究组标准,均接受 4 周 1000mg 剂量的治疗,随后每 8 周接受 4 次扩展诱导剂量。主要终点是 1000mg 治疗的总缓解率(ORR);次要终点是无进展生存期(PFS)和安全性。共纳入 51 例患者。15 例患者随机接受 500mg 治疗,因入组缓慢而停用该剂量组。在接受 1000mg 治疗的 36 例患者中,ORR 为 84%,中位 PFS 为 1.9 年,中位缓解持续时间为 23.7 个月。所有患者均存活。未发生 4 级输注反应或 3/4 级感染。仅在 1000mg 组发生 25%的 3 级输注反应(均为首次输注);除 2 例外,所有患者均继续研究。总研究人群中有 6%的患者因治疗而停药。在未经治疗的低/中危 FLIPI、晚期 FL 患者中,通过扩展诱导给予奥法妥珠单抗单药治疗具有良好的耐受性和疗效。该药物的疗效似乎与单药利妥昔单抗相似。