4th Department of Internal Medicine-Hematology, Charles University, Hospital and Faculty of Medicine, Hradec Králové, Czech Republic.
Department of Oncology of the 2nd Faculty of Medicine of Charles University and University Hospital in Motol, Prague, Czech Republic.
Blood. 2023 Oct 19;142(16):1348-1358. doi: 10.1182/blood.2023020637.
Anti-CD19 immunotherapy tafasitamab is used in combination with lenalidomide in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant. Open-label, phase 1b, First-MIND study assessed safety and preliminary efficacy of tafasitamab + R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) ± lenalidomide as first-line therapy in patients with DLBCL. From December 2019 to August 2020, 83 adults with untreated DLBCL (International Prognostic Index 2-5) were screened and 66 were randomly assigned (33 per arm) to R-CHOP-tafasitamab (arm T) or R-CHOP-tafasitamab-lenalidomide (arm T/L) for 6 cycles. Primary end point was safety; secondary end points included end-of-treatment (EoT) overall response rate (ORR) and complete response (CR) rate. All patients had ≥1 treatment-emergent adverse event, mostly grade 1 or 2. Grade ≥3 neutropenia and thrombocytopenia occurred, respectively, in 57.6% and 12.1% (arm T) and 84.8% and 36.4% (arm T/L) of patients. Nonhematologic toxicities occurred at similar rates among arms. R-CHOP mean relative dose intensity was ≥89% in both arms. EoT ORR was 75.8% (CR 72.7%) in arm T and 81.8% (CR 66.7%) in arm T/L; best ORR across visits was 90.0% and 93.9%. Eighteen-month duration of response and of CR rates were 72.7% and 74.5% (arm T) and 78.7% and 86.5% (arm T/L); 24-month progression-free and overall survival rates were 72.7% and 90.3% (arm T) and 76.8% and 93.8% (arm T/L). Manageable safety and promising signals of efficacy were observed in both arms. Potential benefit of adding tafasitamab + lenalidomide to R-CHOP is being investigated in phase 3 frontMIND (NCT04824092). This study is registered at www.clinicaltrials.gov as #NCT04134936.
抗 CD19 免疫疗法 tafasitamab 与来那度胺联合用于不适合自体干细胞移植的复发性/难治性弥漫性大 B 细胞淋巴瘤 (DLBCL) 患者。开放标签、1b 期 First-MIND 研究评估了 tafasitamab + R-CHOP（利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松）±来那度胺作为未经治疗的 DLBCL 患者一线治疗的安全性和初步疗效。2019 年 12 月至 2020 年 8 月，筛选了 83 名未经治疗的 DLBCL（国际预后指数 2-5）成年患者，其中 66 名随机分配（每组 33 名）至 R-CHOP-tafasitamab（T 组）或 R-CHOP-tafasitamab-来那度胺（T/L 组）进行 6 个周期的治疗。主要终点为安全性；次要终点包括治疗结束（EoT）时的总缓解率（ORR）和完全缓解率（CR）。所有患者均发生了≥1 次治疗后出现的不良事件，大多数为 1 级或 2 级。分别有 57.6%（T 组）和 84.8%（T/L 组）的患者发生了≥3 级中性粒细胞减少症和血小板减少症，分别有 12.1%（T 组）和 36.4%（T/L 组）的患者发生了上述情况。各治疗组发生的非血液学毒性反应的发生率相似。在两个治疗组中，R-CHOP 的平均相对剂量强度均≥89%。T 组的 EoT ORR 为 75.8%（CR 为 72.7%），T/L 组为 81.8%（CR 为 66.7%）；最佳缓解率在各个访视点分别为 90.0%和 93.9%。T 组和 T/L 组的 18 个月缓解持续时间和 CR 率分别为 72.7%和 74.5%（T 组）和 78.7%和 86.5%（T/L 组）；24 个月时无进展生存率和总生存率分别为 72.7%和 90.3%（T 组）和 76.8%和 93.8%（T/L 组）。在两个治疗组中均观察到了可管理的安全性和有希望的疗效信号。正在 3 期 frontMIND 研究（NCT04824092）中进一步评估 tafasitamab + 来那度胺联合 R-CHOP 的潜在获益。这项研究在 ClinicalTrials.gov 注册，编号为 #NCT04134936。
