美国梅奥诊所Mark R. Litzow团队研究了博纳吐单抗治疗成人MRD阴性急性淋巴母细胞白血病的疗效与安全性。相关论文于2024年7月25日发表在《新英格兰医学杂志》上。

许多患有B细胞前体急性淋巴母细胞白血病（BCP-ALL）的老年人尽管有可测量的残余疾病（MRD）——联合化疗的阴性完全缓解，但还是复发了。添加博纳吐单抗（一种双特异性T细胞接合剂分子）已被批准用于治疗复发、难治性和MRD阳性的BCP-ALL，可能对MRD阴性缓解的患者有效。

在一项3期试验中，研究组随机分配了30至70岁BCR:ABL1阴性BCP-ALL（用：：表示融合）的患者，这些患者在诱导和强化化疗后MRD阴性缓解（定义为流式细胞术评估的骨髓中<0.01%的白血病细胞），除四个周期的巩固化疗外，还接受四个疗程的博纳吐单抗治疗，或单独接受四个周期巩固化疗。主要终点是总生存期，无复发生存期是次要终点。

数据和安全性监测委员会审查了第三次疗效中期分析的结果，并建议报告这些结果。488名入选患者中有395名（81%）观察到完全缓解，伴或不伴完全计数恢复。在224名MRD阴性患者中，每组112名。两组患者的特征是平衡的。在43个月的中位随访中，与仅接受化疗的组相比，博纳吐单抗组在总体生存率方面具有优势（3年：85%对68%；死亡风险比为0.41；95%置信区间[CI]为0.23至0.73；P=0.002），博纳吐单抗组的3年无复发生存率为80%，仅接受化疗组为64%（复发或死亡风险比，0.53；95%CI，0.32至0.87）。据报道，博纳吐单抗组的神经精神事件发生率高于仅化疗组。

研究结果表明，在BCP-ALL MRD阴性缓解的成年患者中，在巩固化疗中加入博纳吐单抗显著提高了总体生存率。

附：英文原文

Title: Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults

Author: Mark R. Litzow, Zhuoxin Sun, Ryan J. Mattison, Elisabeth M. Paietta, Kathryn G. Roberts, Yanming Zhang, Janis Racevskis, Hillard M. Lazarus, Jacob M. Rowe, Daniel A. Arber, Matthew J. Wieduwilt, Michaela Liedtke, Julie Bergeron, Brent L. Wood, Yaqi Zhao, Gang Wu, Ti-Cheng Chang, Wenchao Zhang, Keith W. Pratz, Shira N. Dinner, Noelle Frey, Steven D. Gore, Bhavana Bhatnagar, Ehab L. Atallah, Geoffrey L. Uy, Deepa Jeyakumar, Tara L. Lin, Cheryl L. Willman, Daniel J. DeAngelo, Shejal B. Patel, Michelle A. Elliott, Anjali S. Advani, Dimitrios Tzachanis, Pankit Vachhani, Rupali R. Bhave, Elad Sharon, Richard F. Little, Harry P. Erba, Richard M. Stone, Selina M. Luger, Charles G. Mullighan, Martin S. Tallman

Issue&Volume: 2024-07-25

Abstract:

BACKGROUND

Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)–negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.

METHODS

In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with BCR::ABL1-negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.01% leukemic cells in bone marrow as assessed on flow cytometry) after induction and intensification chemotherapy to receive four cycles of blinatumomab in addition to four cycles of consolidation chemotherapy or to receive four cycles of consolidation chemotherapy alone. The primary end point was overall survival, and relapse-free survival was a secondary end point.

RESULTS

The data and safety monitoring committee reviewed the results from the third efficacy interim analysis and recommended that they be reported. Complete remission with or without full count recovery was observed in 395 of 488 enrolled patients (81%). Of the 224 patients with MRD-negative status, 112 were assigned to each group. The characteristics of the patients were balanced between the groups. At a median follow-up of 43 months, an advantage was observed in the blinatumomab group as compared with the chemotherapy-only group with regard to overall survival (at 3 years: 85% vs. 68%; hazard ratio for death, 0.41; 95% confidence interval [CI], 0.23 to 0.73; P=0.002), and the 3-year relapse-free survival was 80% with blinatumomab and 64% with chemotherapy alone (hazard ratio for relapse or death, 0.53; 95% CI, 0.32 to 0.87). A higher incidence of neuropsychiatric events was reported in the blinatumomab group than in the chemotherapy-only group.

CONCLUSIONS

The addition of blinatumomab to consolidation chemotherapy in adult patients in MRD-negative remission from BCP-ALL significantly improved overall survival.

DOI: NJ202407253910408

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2312948