Kugler Eitan, Kantarjian Hagop, Jabbour Elias, Khaire Niranjan, Short Nicholas J, Kadia Tapan M, Haddad Fadi G, Sasaki Koji, Kanagal Shamanna Rashmi, Garris Rebecca, Ravandi Farhad, Jain Nitin
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cancer. 2025 Mar 1;131(5):e35773. doi: 10.1002/cncr.35773.
The BCR::ABL1 tyrosine kinase inhibitors (TKIs) have significantly improved the outcomes of patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, the optimal duration of TKI therapy in patients who achieve a complete molecular response (CMR; undetectable BCR::ABL1 transcripts) and who do not undergo allogeneic stem cell transplantation (allo-SCT) remains undefined.
The authors conducted a retrospective analysis of patients with Ph-positive ALL in first complete remission who achieved a CMR and discontinued TKI therapy, most commonly due to treatment-related side effects.
In total, 14 patients were identified. The regimen of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine was the primary backbone chemotherapy and was received by 12 patients (86%) combined with either imatinib (14%), dasatinib (43%), or ponatinib (29%) during induction. Two patients received blinatumomab and ponatinib. The median duration of TKI therapy was 60 months. The median CMR duration before TKI discontinuation was 46.1 months (range, 2.7-121.3 months). After a median follow-up of 42.5 months from TKI discontinuation, three patients (21%) experienced relapse (two molecular, one morphologic), whereas 11 patients (79%) maintained treatment-free remission. The median time to relapse was 6.4 months (range, 4-16 months), and two of three relapsed patients regained CMR after resuming TKI therapy. Importantly, none of the six patients with a CMR duration >48 months before TKI discontinuation relapsed.
The current findings suggest that TKI discontinuation may be safe for highly selected patients with Ph-positive ALL in first complete remission who maintain CMR for at least 48 months. Larger studies are needed to confirm these findings.
BCR::ABL1酪氨酸激酶抑制剂（TKIs）显著改善了费城染色体（Ph）阳性急性淋巴细胞白血病（ALL）患者的治疗结局。然而，对于达到完全分子缓解（CMR；BCR::ABL1转录本检测不到）且未接受异基因干细胞移植（allo-SCT）的患者，TKI治疗的最佳持续时间仍不明确。
作者对首次完全缓解且达到CMR并停用TKI治疗（最常见原因是治疗相关副作用）的Ph阳性ALL患者进行了回顾性分析。
共纳入14例患者。超分割环磷酰胺、长春新碱、阿霉素和地塞米松与大剂量甲氨蝶呤和阿糖胞苷交替使用的方案是主要的巩固化疗方案，12例患者（86%）接受了该方案，诱导期联合使用伊马替尼（14%）、达沙替尼（43%）或波纳替尼（29%）。2例患者接受了博纳吐单抗和波纳替尼治疗。TKI治疗的中位持续时间为60个月。停用TKI前CMR的中位持续时间为46.1个月（范围2.7 - 121.3个月）。从停用TKI开始中位随访42.5个月后，3例患者（21%）复发（2例分子复发，1例形态学复发），而11例患者（79%）维持无治疗缓解状态。复发的中位时间为6.4个月（范围4 - 16个月），3例复发患者中有2例在恢复TKI治疗后再次达到CMR。重要的是，停用TKI前CMR持续时间>48个月的6例患者均未复发。
目前的研究结果表明，对于首次完全缓解且CMR至少维持48个月的高度选择的Ph阳性ALL患者，停用TKI可能是安全的。需要更大规模的研究来证实这些发现。
