Department Hematology and Oncology, Medical Faculty, University of Augsburg, Augsburg, Germany.
Service d'Hématologie et de Thérapie cellulaire, Hôpital Saint Antoine, ALWP Office (EBMT), Paris, France.
Bone Marrow Transplant. 2021 May;56(5):1190-1199. doi: 10.1038/s41409-020-01173-x. Epub 2020 Dec 9.
Second- and third-generation tyrosine kinase inhibitors (TKI) play an important role in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, data on feasibility and efficacy of using these drugs for persisting or relapsed Ph + ALL after allogeneic stem cell transplantation (alloSCT) are scarce. Based on the EBMT Acute Leukemia Working Party registry, we evaluated the use of second-/third-generation TKI in 140 patients with Ph + ALL, suffering from measurable residual disease (MRD, n = 6), molecular relapse (MRel, n = 23), or hematological relapse (HRel, n = 111) following alloSCT. Treatment included dasatinib in 104, nilotinib in 18, or ponatinib in 18 patients. Forty-nine patients received TKI monotherapy, while 91 received additional treatment. Toxicity of second-/third-generation TKI post alloSCT was comparable to pretransplant use and could be managed with dose reduction or temporary discontinuation. Response rates were 71% (overall) and 61% (following TKI monotherapy). For the entire cohort, 2- and 5-year overall survival (OS) was 49% and 33%, respectively. OS was comparable among patients treated for persisting MRD/MRel and HRel. Among patients treated with TKI monotherapy, 2- and 5-year OS was 38% and 33%, respectively. The data underscore that second-/third-generation TKI are important compounds for the management of active Ph + ALL post alloSCT.
第二代和第三代酪氨酸激酶抑制剂（TKI）在治疗费城染色体阳性急性淋巴细胞白血病（Ph+ALL）中发挥着重要作用。然而，关于这些药物在异基因造血干细胞移植（alloSCT）后用于持续性或复发性 Ph+ALL 的可行性和疗效的数据却很少。基于 EBMT 急性白血病工作组的注册资料，我们评估了 140 例 Ph+ALL 患者在 alloSCT 后发生可测量残留病（MRD，n=6）、分子复发（MRel，n=23）或血液学复发（HRel，n=111）时使用第二代/第三代 TKI 的情况。治疗包括达沙替尼 104 例、尼洛替尼 18 例或泊那替尼 18 例。49 例患者接受 TKI 单药治疗，91 例患者接受了额外的治疗。alloSCT 后第二代/第三代 TKI 的毒性与移植前使用的毒性相当，可以通过减少剂量或暂时停药来控制。总体缓解率为 71%（全部患者）和 61%（接受 TKI 单药治疗的患者）。对于整个队列，2 年和 5 年总生存率（OS）分别为 49%和 33%。对于治疗持续性 MRD/MRel 和 HRel 的患者，OS 无差异。在接受 TKI 单药治疗的患者中，2 年和 5 年的 OS 分别为 38%和 33%。这些数据强调了第二代/第三代 TKI 是 alloSCT 后治疗持续性 Ph+ALL 的重要药物。
