The administration of TKIs after Allo-SCT in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remains controversial, and the TKI approach (prophylactic, pre-emptive or salvage) is still heterogeneous in transplant centers. In this context, very little is known about the feasibility and safety of third-generation TKIs. In this paper, we analyze the efficacy and safety of ponatinib (PONA) administered after Allo-SCT to prevent cytologic relapse of Ph + ALL. This is a multicenter observational study including 48 patients (pts) with Ph + ALL (median age 49 years) who received PONA after Allo-SCT while in complete cytological remission (cCR); 26 (54%) had positive minimal residual disease (MRD pos) before Allo-SCT. PONA was administered after Allo-SCT prophylactically (starting with MRD neg) in 26 pts or pre-emptively (starting with MRD pos post-SCT and without hematological relapse) in 22 pts. Patients treated prophylactically with PONA started treatment earlier, at a median of 4.3 months (range 1.5–6) after Allo-SCT, than those treated pre-emptively, who started PONA at a median of 7.4 months (range 2–63) after Allo-SCT (p= 0.01). The median starting dose of PONA was 30 mg/day (range 15–45). A dose reduction was required in 10/48 (21%) of cases, but a permanent discontinuation of PONA, due to toxicity, was required in only 5/48 pts (10.5%). No deaths due to PONA-related adverse events (AEs) were reported. The median follow-up time after Allo-SCT was 34 months (range 7.7–118). At the last follow-up, the median duration of PONA therapy was 22 months (range 2–100). The 5-year OS and RFS after Allo-SCT were 92% and 71%, respectively. The 5-year RFS after Allo-SCT of pts who received PONA prophylaxis was 95%, and it was 57% for those who received PONA pre-emptively (log-rankp= 0.02). In conclusion, this multicenter analysis of 48 patients with Ph + ALL undergoing Allo-SCT while in CcR, although with the caution of the retrospective data, supports the feasibility of PONA maintenance strategy after Allo-SCT with a low rate of discontinuations (10.5%) due to PONA-related AE.
费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）患者在接受异基因造血干细胞移植（Allo-SCT）后使用酪氨酸激酶抑制剂（TKIs）的治疗策略仍存在争议，且不同移植中心对TKI的应用方式（预防性、抢先性或挽救性）仍存在差异。在此背景下，关于第三代TKIs的可行性和安全性知之甚少。本文旨在分析Allo-SCT后使用普纳替尼（PONA）预防Ph+ ALL细胞学复发的疗效与安全性。本研究为一项多中心观察性研究，纳入了48例在完全细胞学缓解（cCR）状态下接受Allo-SCT后使用PONA的Ph+ ALL患者（中位年龄49岁）；其中26例（54%）在Allo-SCT前存在微小残留病阳性（MRD阳性）。PONA在Allo-SCT后以预防性方式（起始时MRD阴性）应用于26例患者，或以抢先性方式（起始时为移植后MRD阳性且无血液学复发）应用于22例患者。预防性使用PONA的患者开始治疗时间较早，中位时间为Allo-SCT后4.3个月（范围1.5–6个月），而抢先治疗组开始PONA的中位时间为Allo-SCT后7.4个月（范围2–63个月）（p=0.01）。PONA的起始中位剂量为30毫克/天（范围15–45毫克）。48例患者中有10例（21%）需要减量，但仅5例（10.5%）因毒性需要永久停用PONA。未报告与PONA相关不良事件（AEs）导致的死亡。Allo-SCT后的中位随访时间为34个月（范围7.7–118个月）。至末次随访时，PONA治疗的中位持续时间为22个月（范围2–100个月）。Allo-SCT后5年总生存率（OS）和无复发生存率（RFS）分别为92%和71%。接受PONA预防治疗的患者Allo-SCT后5年RFS为95%，而接受抢先治疗的患者为57%（对数秩检验p=0.02）。总之，这项针对48例在CcR状态下接受Allo-SCT的Ph+ ALL患者的多中心分析，尽管存在回顾性数据的局限性，仍支持Allo-SCT后采用PONA维持策略的可行性，且因PONA相关AE导致的停药率较低（10.5%）。
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