An analysis of the kinetics of molecular response during the first trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia patients in chronic phase

作者：Luis Steegmann Juan; Colomer Dolors; Gomez Casares Maria Teresa; Garcia Gutierrez Valentin; Orti Guillermo; Ramirez Payer Angel; Olavarria Eduardo; Vall llovera Ferran; Giraldo Pilar; Conde Eulogio; Vallansot Rolando; Luis Lopez Lorenzo Jose; Palomera Luis; Alvarez Larran Alberto; Conesa Venancio; Bautista Guiomar; Casas Laura; Giles Frank; Hochhaus Andreas; Felipe Casado Montero Luis

来源：Journal of Cancer Research and Clinical Oncology, 2017, 143(10): 2059-2066.

DOI：10.1007/s00432-017-2445-z

• Chronic myeloid leukemia
• Nilotinib
• ENEST1st

Purpose This study was aimed to analyze the association of very early molecular response to nilotinib with the achievement of deep molecular response (MR4) at 18 months. We hypothesized that the BCR-ABL1 levels during the first 3 months of therapy, and the kinetics of their descent in this period, could be predictive of deep molecular response thereafter.
Methods This substudy of the ENEST1st trial included 60 patients with chronic myeloid leukemia in chronic phase treated with front-line nilotinib, and BCR-ABL1IS levels were measured using GUS as the control gene. The analysis included seven time points during the first trimester of treatment (baseline and fortnightly thereafter).
Results The rates of MMR at 12 months, and of MR4 at 18 months (primary variable of the study), were 70 and 41%, respectively, similar to those obtained in the core study. BCR-ABL1IS <= 10% was achieved at 1, 1.5, 2 and 3 months in 50, 70, 83 and 93% of the patients, respectively. The observed shape of the BCR-ABL1IS descent was biphasic, with a faster slope during the first trimester and a median halving time (HT) of 11 days, the shortest reported in the literature. An HT <= 13 days was predictive of MMR at 12 months and MR4 at 18 months.
Conclusions The association of a shorter HT with response provides a rationale for exploring very early kinetics patterns in all patients treated with potent TKIs such as nilotinib.

• 出版日期2017-10
• 单位西北大学