Levis Mark J, Hamadani Mehdi, Logan Brent R, Jones Richard J, Singh Anurag K, Litzow Mark R, Wingard John R, Papadopoulos Esperanza B, Perl Alexander E, Soiffer Robert J, Ustun Celalettin, Ueda Oshima Masumi, Uy Geoffrey L, Waller Edmund K, Vasu Sumithira, Solh Melhem M, Mishra Asmita, Muffly Lori S, Kim Hee-Je, Stelljes Matthias, Najima Yuho, Onozawa Masahiro, Thomson Kirsty J, Chen Caroline, Hasabou Nahla, Rosales Matt, Hill Jason E, Gill Stanley C, Nuthethi Rishita, King Denise, Mendizabal Adam M, Devine Steven M, Horowitz Mary M, Chen Yi-Bin
Johns Hopkins University, Baltimore, Maryland, United States.
Medical College of Wisconsin, Wauwatosa, Wisconsin, United States.
Blood Adv. 2025 Jul 1. doi: 10.1182/bloodadvances.2025016306.
We conducted a post-hoc analysis of data from BMT CTN 1506 (MORPHO), a randomized trial of gilteritinib versus placebo as post-transplantation maintenance for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 co-mutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD-negative pre-HCT, there was no difference in the cumulative incidence of relapse during follow-up between those receiving MAC versus RIC. NPM1 co-mutation was associated with the largest magnitude of relapse-free survival benefit from post-HCT gilteritinib, and in these participants, post-HCT gilteritinib in the setting of RIC appeared to be as effective as MAC at preventing relapse. Only in participants who were NPM1 wild-type at diagnosis and were FLT3-ITD MRD-positive prior to HCT did MAC appear superior to RIC in preventing relapse. Our findings suggest that only a subset of patients with FLT3-ITD AML undergoing HCT may benefit from myeloablative conditioning, and that, much like AML therapy prior to HCT, the intensity of the HCT regimen should be adapted according to the molecular features of the disease. (NCT02997202).
我们对BMT CTN 1506（MORPHO）的数据进行了事后分析，这是一项关于吉瑞替尼与安慰剂作为接受异基因造血细胞移植（HCT）的FLT3-ITD突变急性髓系白血病（AML）患者移植后维持治疗的随机试验，重点关注预处理方案强度、可测量残留病（MRD）和诊断时报告的NPM1共突变状态之间的相互作用。比较预处理前后的FLT3-ITD MRD，清髓性预处理（MAC）和减低强度预处理（RIC）在根除或降低FLT3-ITD MRD方面没有差异。对于HCT前FLT3-ITD MRD阴性的参与者，接受MAC与RIC的患者在随访期间的累积复发率没有差异。NPM1共突变与HCT后使用吉瑞替尼获得的无复发生存获益幅度最大相关，在这些参与者中，RIC方案下的HCT后吉瑞替尼在预防复发方面似乎与MAC一样有效。仅在诊断时为NPM1野生型且HCT前FLT3-ITD MRD阳性的参与者中，MAC在预防复发方面似乎优于RIC。我们的研究结果表明，只有一部分接受HCT的FLT3-ITD AML患者可能从清髓性预处理中获益，并且与HCT前的AML治疗非常相似，HCT方案的强度应根据疾病的分子特征进行调整。（NCT02997202）
