Kantarjian Hagop, Short Nicholas J, Jain Nitin, Haddad Fadi G, Kadia Tapan, Yilmaz Musa, Ferrajoli Alessandra, Sasaki Koji, Alvarado Yesid, Pemmaraju Naveen, Senapati Jayastu, Garris Rebecca, Ravandi Farhad, Jabbour Elias
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Am J Hematol. 2025 Mar;100(3):402-407. doi: 10.1002/ajh.27576. Epub 2025 Jan 5.
Adding inotuzumab ozogamicin (InO) to hyper-CVAD and blinatumomab may improve outcomes in newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL). Patients with newly diagnosed B-ALL received up to four cycles of hyper-CVAD followed by four cycles of blinatumomab. Beginning with patient #39, InO 0.3 mg/m was added on Days 1 and 8 to two cycles of high-dose methotrexate and cytarabine, and two cycles of blinatumomab. The primary endpoint was the relapse-free survival (RFS) rate. Seventy-five patients were treated (median age of 33 years; range, 18-59), of whom 37 (49%) received hyper-CVAD with blinatumomab and InO (cohort 2). Measurable residual disease (MRD) negativity by next-generation sequencing (sensitivity: 1 × 10) was achieved in 79% of patients in cohort 2. The median follow-up was 44 months (range, 13-90) overall, and 26 months (range, 8-39) in cohort 2. For the entire cohort, the estimated 3-year RFS rate was 82% and the 3-year overall survival rate was 90%. These rates were 90% versus 74% (p = 0.06) and 100% versus 82% (p = 0.01) in patients who did or did not receive InO, respectively. No sinusoidal obstruction syndrome was observed. In summary, hyper-CVAD with blinatumomab and InO improved the outcomes of patients with newly diagnosed B-ALL.
在Hyper-CVAD方案中加入奥英妥珠单抗（InO）和博纳吐单抗可能会改善新诊断的费城染色体（Ph）阴性B细胞急性淋巴细胞白血病（B-ALL）的治疗结果。新诊断的B-ALL患者接受了多达四个周期的Hyper-CVAD方案，随后接受四个周期的博纳吐单抗治疗。从第39例患者开始，在第1天和第8天，在两个周期的大剂量甲氨蝶呤和阿糖胞苷以及两个周期的博纳吐单抗治疗中加入0.3mg/m的InO。主要终点是无复发生存率（RFS）。75例患者接受了治疗（中位年龄33岁；范围18-59岁），其中37例（49%）接受了Hyper-CVAD联合博纳吐单抗和InO治疗（队列2）。队列2中79%的患者通过下一代测序（灵敏度：1×10）实现了可测量残留病（MRD）阴性。总体中位随访时间为44个月（范围13-90个月），队列2为26个月（范围8-39个月）。对于整个队列，估计3年RFS率为82%，3年总生存率为90%。接受或未接受InO的患者中，这些比率分别为90%对74%（p=0.06）和100%对82%（p=0.01）。未观察到窦性阻塞综合征。总之，Hyper-CVAD联合博纳吐单抗和InO改善了新诊断B-ALL患者的治疗结果。
