Haddad Fadi G, Sawyers Jacki, Short Nicholas J
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 428, Houston, TX 77030, USA.
Ther Adv Hematol. 2023 Feb 3;14:20406207231151294. doi: 10.1177/20406207231151294. eCollection 2023.
The management of Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) has witnessed major progress over the past two decades. Initially, the incorporation of the first-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) imatinib into intensive chemotherapy regimens improved outcomes compared with chemotherapy alone. The combinations of chemotherapy with second- or third-generation TKIs further improved outcomes, with higher rates of complete molecular remission (CMR) and superior survival. The combination of ponatinib plus chemotherapy resulted in durable remissions and prolonged long-term survival, even in patients who did not receive allogeneic stem cell transplantation (SCT). The promising results seen with later-generation TKIs have caused many to re-evaluate the role of allogeneic SCT for patients who achieve CMR with potent TKI regimens. Recently, the chemotherapy-free combinations of blinatumomab plus TKIs were shown to be safe and effective in newly diagnosed Ph-positive ALL, sparing patients the toxicities associated with intensive chemotherapy. In particular, encouraging early results have been seen with the combination of blinatumomab plus ponatinib, suggesting that this regimen may represent a chemotherapy-free and SCT-sparing strategy for patients with Ph-positive ALL. Herein, we discuss the current evidence for frontline therapies of Ph-positive ALL, the treatment de-escalation strategies over time, and the role of allogeneic SCT in view of the emergence of newer chemotherapy-free regimens using potent TKIs.
在过去二十年中，费城染色体阳性（Ph阳性）急性淋巴细胞白血病（ALL）的管理取得了重大进展。最初，与单纯化疗相比，将第一代BCR::ABL1酪氨酸激酶抑制剂（TKI）伊马替尼纳入强化化疗方案改善了治疗结果。化疗与第二代或第三代TKI的联合进一步改善了治疗结果，完全分子缓解（CMR）率更高，生存率更高。泊那替尼联合化疗即使在未接受异基因干细胞移植（SCT）的患者中也能产生持久缓解并延长长期生存期。新一代TKI取得的令人鼓舞的结果促使许多人重新评估异基因SCT对通过强效TKI方案实现CMR的患者的作用。最近，在新诊断的Ph阳性ALL中，博纳吐单抗联合TKI的无化疗组合被证明是安全有效的，使患者免受强化化疗相关的毒性影响。特别是，博纳吐单抗联合泊那替尼的组合取得了令人鼓舞的早期结果，表明该方案可能代表了一种针对Ph阳性ALL患者的无化疗和无需SCT的策略。在此，我们讨论Ph阳性ALL一线治疗的当前证据、随着时间推移的治疗降阶梯策略以及鉴于使用强效TKI的新型无化疗方案的出现，异基因SCT的作用。
