Haddad Fadi G, Kantarjian Hagop, Senapati Jayastu, Jain Nitin, Short Nicholas J, Jabbour Elias
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Clin Lymphoma Myeloma Leuk. 2025 Jun 26. doi: 10.1016/j.clml.2025.06.019.
The incorporation of ponatinib into the frontline regimens of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) deepened the molecular responses and improved outcomes. Patients with Ph-positive ALL who achieve a complete molecular response (CMR, undetectable BCR::ABL1 transcripts by RT-PCR) by 3 months of therapy have a better survival compared to those with persistent disease. Studies showed that the next-generation sequencing (NGS) assay, with a sensitivity up to 1 × 10, is more sensitive than RT-PCR for the detection of measurable residual disease (MRD) in Ph-positive ALL and therefore carries a better prognostic value. Patients who achieve a 3-month CMR and undetectable MRD by NGS have excellent outcomes and may not need consolidation with allogeneic hematopoietic stem cell transplantation (HSCT) in first remission. However, omitting HSCT in certain patients with high-risk disease features, such as IKZF1, remains to be determined. Outcomes were significantly improved with the combination of blinatumomab and ponatinib. This chemotherapy-free regimen resulted in a CMR rate of 80% by RT-PCR and 99% by NGS, with a 3-year overall survival rate of 89%. Only 2 of 76 patients (3%) underwent HSCT in this study. Combinations of newer TKIs (such as asciminib or olverembatinib) with blinatumomab (intravenous, subcutaneous) might further improve outcomes and are being explored. Achieving durable NGS MRD negativity can identify patients at low risk of relapse who might be candidates for treatment discontinuation. In this review, we discuss the current progress in the management of Ph-positive ALL, particularly the role of chemotherapy-free regimens in mitigating the need for HSCT.
将波纳替尼纳入费城染色体（Ph）阳性急性淋巴细胞白血病（ALL）的一线治疗方案可加深分子反应并改善预后。接受治疗3个月时达到完全分子反应（CMR，通过逆转录聚合酶链反应检测不到BCR::ABL1转录本）的Ph阳性ALL患者比疾病持续存在的患者生存率更高。研究表明，灵敏度高达1×10的下一代测序（NGS）检测在检测Ph阳性ALL的可测量残留病（MRD）方面比逆转录聚合酶链反应更敏感，因此具有更好的预后价值。通过NGS在3个月时达到CMR且检测不到MRD的患者预后极佳，在首次缓解时可能无需进行异基因造血干细胞移植（HSCT）巩固治疗。然而，对于某些具有高风险疾病特征（如IKZF1）的患者，是否省略HSCT仍有待确定。博纳吐单抗与波纳替尼联合使用可显著改善预后。这种无化疗方案通过逆转录聚合酶链反应的CMR率为80%，通过NGS为99%，3年总生存率为89%。在本研究中，76例患者中只有2例（3%）接受了HSCT。新型酪氨酸激酶抑制剂（如阿西替尼或奥雷巴替尼）与博纳吐单抗（静脉注射、皮下注射）联合使用可能会进一步改善预后，目前正在进行探索。实现持久的NGS MRD阴性可识别复发风险低的患者，这些患者可能是停止治疗的候选者。在本综述中，我们讨论了Ph阳性ALL治疗的当前进展，特别是无化疗方案在减少HSCT需求方面的作用。
