Murbach Bruna, Duarte Gislaine, Palma Leonardo Carvalho, Miranda Eliana, Duffles Guilherme, Furlin Graziele Pavan, Toni Isabella, De Souza Carmino, Binelli Larissa, Bassan Vitor Leonardo, de Castro Fabiola Attie, de Figueiredo-Pontes Lorena Lobo, Pagnano Katia Borgia Barbosa
Centro de Hematologia e Hemoterapia (Hemocentro-UNICAMP), Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Hematology Division, Department of Medical Images, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Front Oncol. 2024 May 8;14:1393191. doi: 10.3389/fonc.2024.1393191. eCollection 2024.
Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of patients with chronic myeloid leukemia. Patients who achieve sustained deep molecular response are eligible for treatment discontinuation. DES-CML is an ongoing, phase 2 multicentric discontinuation trial. Adult patients with CML in chronic phase with typical transcripts, stable deep molecular response (MR4.5 IS) for two years, and no previous resistance were eligible. Patients underwent a phase of TKI dose de-escalation for six months before discontinuation. TKI was reintroduced at the previous dose if the patient lost major molecular response (MMR) at any time. This study aimed to assess the impact of BCR-ABL transcript kinetics during TKI de-escalation and discontinuation phases on treatment-free survival. So far, the study recruited 41 patients, and 38 patients discontinued therapy (4 were in the second discontinuation attempt). Eleven patients lost MMR, one during the de-escalation phase and ten after discontinuation. 24-month treatment-free survival was 66% (95% CI: 48-84%) in a median follow-up of 7 (1-30) months. No patient lost hematological response or had disease progression. A higher rate of molecular relapses occurred in patients with fluctuating levels after the discontinuation phase (with loss of MR4.5, but no loss of MMR) (P=0.04, HR-4.86 (1.03-22.9) but not confirmed in the multivariate analysis. The longer duration of TKI treatment (P=0.03, HR-1.02, 95%CI - 1.00-1.04) and MMR (P=0.004, HR-0.95, 95%CI - 0.92-098) were independent factors of a lower relapse rate.
酪氨酸激酶抑制剂（TKI）彻底改变了慢性髓性白血病患者的治疗方式。实现持续深度分子反应的患者有资格停药。DES-CML是一项正在进行的2期多中心停药试验。符合条件的成年慢性期CML患者具有典型转录本、两年稳定的深度分子反应（MR4.5 IS）且既往无耐药史。患者在停药前接受为期六个月的TKI剂量递减阶段。如果患者在任何时间失去主要分子反应（MMR），则以先前剂量重新引入TKI。本研究旨在评估TKI剂量递减和停药阶段BCR-ABL转录本动力学对无治疗生存期的影响。到目前为止，该研究招募了41名患者，38名患者停止治疗（4名处于第二次停药尝试中）。11名患者失去MMR，1名在剂量递减阶段，10名在停药后。在中位随访7（1 - 30）个月时，24个月无治疗生存率为66%（95%CI：48 - 84%）。没有患者失去血液学反应或出现疾病进展。在停药阶段后水平波动（失去MR4.5，但未失去MMR）的患者中分子复发率较高（P = 0.04，HR - 4.86（1.03 - 22.9），但在多变量分析中未得到证实。TKI治疗持续时间较长（P = 0.03，HR - 1.02，95%CI - 1.00 - 1.04）和MMR（P = 0.004，HR - 0.95，95%CI - 0.92 - 098）是较低复发率的独立因素。
