Long‐term results of frontline dasatinib in chronic myeloid leukemia

Abstract

Background Dasatinib is a second‐generation tyrosine kinase inhibitor that, when used as frontline therapy, produces more and faster cytogenetic and molecular responses compared with imatinib. The authors report the long‐term follow‐up from the first study using dasatinib as initial therapy for chronic‐phase chronic myeloid leukemia. Methods Between November 2005 and August 2014, patients were randomly assigned to receive 100 mg daily or 50 mg twice daily. After June 2009, all patients started with 100 mg daily. Results With a median follow‐up of 6.5 years, 94 of 149 treated patients (63%) were still receiving dasatinib on study. The median patient age was 48 years (interquartile range, 37‐55 years), and 9% of patients had a high risk Sokal risk score. The cumulative complete cytogenetic response rate at 11 years was 92.6%, the major molecular response (MR) rate was 88.2%, and the MR4.5 rate (indicating a ≥4.5‐log reduction in BCR‐ABL1 transcripts) was 79.5%. The median time to a major MR and MR4.5 was 6 and 23 months, respectively. A sustained MR4.5 (≥2 years) was achieved in 82 patients (55%). The 10‐year overall survival, transformation‐free survival, event‐free survival, and failure‐free survival rates were 89%, 95%, 86%, and 65%, respectively. Univariate analysis showed that the achievement of a complete MR was associated with improved overall survival. The most common reasons for treatment discontinuation were toxicity and elective discontinuation. The most common treatment‐emergent grade 3 and 4 adverse events were fatigue, thrombocytopenia, and infections. Conclusions After this long‐term follow‐up, dasatinib continues to show an excellent safety profile and produces rapid cytogenetic responses and MRs, durable deep MRs, and excellent long‐term survival outcomes in patients with chronic‐phase chronic myeloid leukemia.

Arterial Hypertension and Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Systematic Review and Meta-Analysis

“…In contrast, only two retrospective articles have analyzed patients treated with subsequent lines ( Caocci et al, 2019a ; García-Gutiérrez et al, 2019 ). Almost all the detected studies on dasatinib were clinical trials considering patients on the first or second line of treatment ( Maiti et al, 2020 ; Bristol-Myers Squibb, 2016 ; Bristol-Myers Squibb, 2015 ( clinicaltrials, (2021). Im, 2021 ; Kantarjian et al, 2009 ).…”

Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring

“…52 The long-term results of frontline nilotinib and dasatinib therapy were reported as well. 53,54 Among 122 patients treated with nilotinib with a median follow-up of 78 months, the cumulative CCyR and MMR rates were 91%, each. Seventy-five percent and 59% of patients achieved MR4.5 and a sustained MR4.5 beyond 2 years, respectively.…”

The CoV-2 outbreak: how hematologists could help to fight Covid-19

“…In multivariate analysis, a previous skin rash or history of autoimmune disease resulted as significant factors predicting pleural effusion [63]. About infective risk during Dasatinib administration, the incidence of grade 3/4 infections resulted 11 % [64]; in the DASISION trial, which compared Dasatinib with Imatinib as first-line treatment, 4.5 % of patients in the Dasatinib and lessa than 1% in the Imatinib cohort died for infections, so sustaining the high infective risk of Dasatinib in comparison to Imatinib [65]. At the moment, no studies with Dasatinib in COVID-19 have been registered in the "clinical trials.gov" website.…”