维奈克拉联合奥加伊妥珠单抗治疗复发难治性急性淋巴细胞白血病
Venetoclax plus Inotuzumab Ozogamicin for Relapsed and Refractory Acute Lymphoblastic Leukemia
复发或难治性B细胞急性淋巴细胞白血病（B-ALL）和淋巴母细胞淋巴瘤（LBL）中，CD22抗体偶联药物奥加伊妥珠单抗虽常有效，但缓解持续时间短。基于临床前协同作用证据，研究者开展1期试验，给成人患者用BCL-2抑制剂维奈克拉联合标准剂量奥加伊妥珠单抗，共23例。推荐剂量为维奈克拉400毫克/天连用21天。未出现剂量限制毒性和早期死亡；最常见的3级以上不良事件为血小板减少（43.5%）和中性粒细胞减少（39.1%），4例出现肝静脉阻塞综合征。22例可评估患者中21例（95.5%）完全缓解，大部分微小残留病转阴，14例后续接受造血干细胞移植。两年无病生存率和总生存率为48%，中位无病生存22.1个月，中位总生存未达到。
为什么推荐给您：两药协同用于复发难治B-ALL/LBL的早期人体试验，缓解与微小残留病清除率高，但样本小、属1期。
不需要生物学背景，多打比方
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摘要Abstract
In relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL), responses to the CD22 antibody-drug conjugate inotuzumab ozogamicin (INO) are frequent but short-lived. Based on preclinical evidence of synergy, we conducted a phase 1 trial of the BCL-2 inhibitor venetoclax (VEN) plus standard-dose INO for adults with R/R CD22+ ALL/LBL. Twenty-three patients enrolled (15 ALL, 8 LBL): three at dose level 1 (DL1; VEN 200 mg/day), six at DL2 (VEN 400 mg/day), and fourteen in an expansion cohort (VEN 400 mg/day). The recommended dose was VEN 400 mg/day for 21 days per cycle. No dose-limiting toxicities or early mortality occurred. Patients received a median of 2 cycles (range 1-5). The most common grade ³3 adverse events were thrombocytopenia (43.5%) and neutropenia (39.1%). Four patients (17.4%) developed sinusoidal obstructive syndrome. Of 22 evaluable patients, 21 (95.5%) achieved complete remission, including 19 after one cycle. Measurable residual disease (MRD) cleared in 16/18 (88.9%) by flow cytometry (<10-4) and 14/19 (73.7%) by next-generation sequencing (<10-6). Fourteen (63.6%) patients proceeded to HSCT. With a median follow-up of 25.3 months (95% CI 19.0-32.4), two-year disease-free (DFS) and overall survival (OS) were 48% (95% CI 24-72%); median DFS was 22.1 months (95% CI 10.4-NA), and median OS was not reached. MRD-positivity was associated with lower baseline BCL-2 dependence. Correlates of progression included acquired MCL-1 dependence, CD22 antigen escape, drug efflux gene ABCB1 expression, and oncogenic mutations. In summary, VEN+INO is safe and effective for R/R B-ALL/LBL, producing frequent and durable MRD-negative remissions. NCT05016947.