PO.ET02.13 · 实验与分子治疗
用于治疗血液系统恶性肿瘤的抗体-药物偶联物
Antibody-drug conjugates for the treatment of hematologic malignancies
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
Belantamab mafodotin由靶向BCMA的单克隆抗体组成，并偶联细胞毒性载荷单甲基auristatin F（MMAF，一种微管破坏剂），已获批用于多发性骨髓瘤。其疗效在DREAMM-7中进行了评估，这是一项针对既往至少接受过一线治疗的复发/难治性（R/R）多发性骨髓瘤成人患者的开放标签、随机试验。BVd组的mPFS为31.3个月（95% CI：23.5，NR），DVd组为10.4个月（95% CI：7，13.4）（HR 0.31，95% CI：0.21，0.47）。两组的mOS分别为NR和35.7个月（95% CI：21.1，NR）（HR 0.49，95% CI：0.32，0.76）。Gemtuzumab ozogamicin靶向髓系细胞上的CD33受体，已获批用于AML。其与化疗（CT）联合用于成人的获批基于ALFA-0701，这是一项针对271例新诊断原发性AML患者的多中心、随机、开放标签3期研究。第二项试验MyloFrance-1是一项2期、单臂、开放标签研究，纳入了57例首次复发的CD33阳性AML患者。15例（26%；95% CI：16%-40%）患者在单疗程gemtuzumab ozogamicin治疗后达到完全缓解（CR）。Inotuzumab ozogamicin靶向B细胞前体白血病细胞上的CD22受体，已获批用于R/R CD22阳性B细胞前体ALL的儿科患者。其疗效在一项多中心、单臂、开放标签研究中进行评估，主要疗效结局指标为完全缓解（CR）、CR持续时间以及达到MRD阴性CR的患者比例。CR定义为骨髓中原始细胞<5%、外周血无白血病原始细胞、外周血计数完全恢复以及任何髓外疾病消退。MRD定义为白血病细胞占骨髓有核细胞的<1×10-4（<0.01%）。22/53（42%，95% CI：28.1，55.9%）达到CR，CR的中位持续时间为8.2个月（95% CI：2.6，NE）。在达到CR的患者中，基于流式细胞术的MRD阴性率为21/22[95.5%（95% CI：77.2，99.9）]，基于RQ-PCR的为19/22[86.4%（95% CI：65.1，97.1）]。Brentuximab vedotin由靶向CD20抗原的单克隆抗体组成，并偶联微管破坏剂单甲基auristatin作为载荷，用于慢性霍奇金淋巴瘤。其获批基于ECHELON-3，这是一项随机、双盲、安慰剂对照试验，纳入了230例不适合接受自体造血干细胞移植（auto-HSCT）或CAR T细胞治疗的R/R大B细胞淋巴瘤（LBCL）成人患者。主要疗效结局指标为OS。其他疗效结局指标包括PFS和ORR。该试验显示OS、PFS和ORR均有统计学意义的改善。BV+R2组的mOS为13.8个月（95% CI：10.3，18.8），Pbo+R2组为8.5个月（95% CI：5.4，11.7）（HR 0.63，95% CI：0.45，0.89）。BV+R2的mPFS为4.2个月（95% CI：2.9，7.1），Pbo+R2为2.6个月（95% CI：1.4，3.1）（HR 0.53，95% CI：0.38，0.73）。ORR分别为64.3%（95% CI：54.7，73.1）和41.5%（95% CI：32.5，51.0）。
查看英文原文 English abstract
Belantamab mafodotin is composed of a monoclonal antibody targeting BCMA and is conjugated to the cytotoxic payload monomethyl auristatin F (MMAF), a microtubule disrupting agent, and is approved for multiple myeloma. Its efficacy was evaluated in DREAMM-7, an open-label, randomized trial in adults with R/R multiple myeloma with at least one prior therapy. The mPFS was 31.3 months (95% CI: 23.5, NR) in the BVd arm and 10.4 months (95% CI: 7, 13.4) in the DVd arm (HR 0.31, 95% CI: 0.21, 0.47). The mOS was NR and 35.7 months (95% CI: 21.1, NR) in respective arms (HR 0.49, 95% CI: 0.32, 0.76). Gemtuzumab oxogamicin targets the CD33 receptor on myeloid cells and is approved for AML. Its approval in combination with CT for adults was based on ALFA-0701, a multicenter, randomized, open-label phase 3 study of 271 patients with newly-diagnosed, de novo AML. The second trial, MyloFrance-1, a phase 2, single-arm, open-label study, included 57 patients with CD33-positive AML in first relapse. Fifteen (26%; 95% CI: 16% - 40%) patients achieved CR following a single course of gemtuzumab ozogamicin. Inotuzumab ozogamicin targets the CD22 receptor on B-cell precursor leukemic cells and is approved for ALL in pediatric patients with R/R CD22-positive B-cell precursor ALL. Efficacy was evaluated in a multicenter, single-arm, open-label study and the main efficacy outcome measures were complete remission (CR), duration of CR, and the proportion of patients with MRD negative CR. CR was defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukemia blasts, full recovery of peripheral blood counts and resolution of any extramedullary disease. MRD was defined by leukemic cells comprising < 1 × 10-4 (<0.01%) of bone marrow nucleated cells. 22/53 (42%, 95% CI: 28.1, 55.9%) achieved CR and the median duration of CR was 8.2 months (95% CI: 2.6, NE). The MRD negativity rate in patients with CR was 21/22 [95.5% (95% CI: 77.2, 99.9)] based on flow cytometry, and 19/22 [86.4% (95% CI: 65.1, 97.1] based on RQ-PCR. Brentuximab vedotin is composed of a monoclonal antibody targeting the CD20 antigen and conjugated to microtubule disrupting agent monomethyl auristatin, which serves as the payload, for chronic Hodgkin's lymphoma. Approval was based on ECHELON-3, a randomized, double-blind, placebo-controlled trial enrolling 230 adult patients with R/R LBCL who were ineligible to receive an auto-HSCT or CAR T-cell therapy. The major efficacy outcome measure was OS. Additional efficacy outcome measures included PFS and ORR. The trial demonstrated a statistically significant improvement in OS, PFS and ORR. mOS of 13.8 months (95% CI: 10.3, 18.8) in the BV+R2 arm and 8.5 months (95% CI: 5.4, 11.7) in the Pbo+R2 arm (HR 0.63, 95% CI: 0.45, 0.89) were shown. mPFS was 4.2 months (95% CI: 2.9, 7.1) with BV+R2 and 2.6 months (95% CI: 1.4, 3.1) with Pbo+R2 (HR 0.53, 95% CI: 0.38, 0.73). The ORR was 64.3% (95% CI: 54.7, 73.1) and 41.5% (95% CI: 32.5, 51.0), respectively.
利益披露 Disclosure
P. Hays, None.