Sartor C, Brunetti L, Audisio E, Cignetti A, Zannoni L, Cristiano G, Nanni J, Ciruolo R, Zingarelli F, Ottaviani E, Patuelli A, Bandini L, Forte D, Sciabolacci S, Cardinali V, Papayannidis C, Cavo M, Martelli M P, Curti A
Dipartimento di Scienze Mediche e Chirurgiche, Istituto di Ematologia "Seràgnoli", Università degli Studi di Bologna, Bologna, Italy.
Clinica di Ematologia, Azienda Ospedaliero-Universitaria Ospedali Riuniti delle Marche, Ancona, Italy.
Br J Haematol. 2023 Aug;202(3):599-607. doi: 10.1111/bjh.18887. Epub 2023 May 24.
NPM1-mutated acute myeloid leukaemia (NPM1 AML) represents a mostly favourable/intermediate risk disease that benefits from allogeneic haematopoietic stem cell transplantation (HSCT) in case of measurable residual disease (MRD) relapse or persistence after induction chemotherapy. Although the negative prognostic role of pre-HSCT MRD is established, no recommendations are available for the management of peri-transplant molecular failure (MF). Based on the efficacy data of venetoclax (VEN)-based treatment in NPM1 AML older patients, we retrospectively analysed the off-label combination of VEN plus azacitidine (AZA) as bridge-to-transplant strategy in 11 NPM1 MRD-positive fit AML patients. Patients were in MRD-positive complete remission (CR ) at the time of treatment: nine in molecular relapse and two in molecular persistence. After a median number of two cycles (range 1-4) of VEN-AZA, 9/11 (81.8%) achieved CR -negative (CR ). All 11 patients proceeded to HSCT. With a median follow-up from treatment start of 26 months, and a median post-HSCT follow-up of 19 months, 10/11 patients are alive (1 died from non-relapse mortality), and 9/10 patients are in MRD status. This patient series highlights the efficacy and safety of VEN-AZA to prevent overt relapse, achieve deep responses and preserve patient fitness before HSCT, in patients with NPM1 AML in MF.
NPM1 突变型急性髓系白血病（NPM1 AML）大多属于预后较好/中等风险的疾病，在诱导化疗后出现可测量残留病（MRD）复发或持续存在的情况下，异基因造血干细胞移植（HSCT）对其有益。尽管HSCT前MRD的负面预后作用已得到确立，但对于移植周围分子学失败（MF）的管理尚无相关建议。基于维奈克拉（VEN）为基础的治疗在老年NPM1 AML患者中的疗效数据，我们回顾性分析了VEN联合阿扎胞苷（AZA）作为桥接移植策略在11例NPM1 MRD阳性的适合AML患者中的应用。治疗时患者处于MRD阳性完全缓解（CR）状态：9例处于分子学复发，2例处于分子学持续存在。经过中位2个周期（范围1 - 4个周期）的VEN - AZA治疗后，9/11（81.8%）患者达到CR阴性（CR）。所有11例患者均接受了HSCT。从治疗开始的中位随访时间为26个月，HSCT后的中位随访时间为19个月，11例患者中有10例存活（1例死于非复发死亡率），10例存活患者中有9例处于MRD状态。该患者系列突出了VEN - AZA在MF的NPM1 AML患者中预防明显复发、实现深度缓解以及在HSCT前保持患者身体状况方面的疗效和安全性。
