Long term follow-up of frontline Dasatinib in older patients with chronic myeloid leukemia in chronic phase treated outside clinical trials: a real-life cohort observational study

Acta Oncol. 2021 Nov;60(11):1527-1533. doi: 10.1080/0284186X.2021.1971292. Epub 2021 Sep 9.

Abstract

Background: A limited amount of data has been published in chronic-phase chronic myeloid leukemia (CP-CML) patients aged >75 years treated frontline with second-generation tyrosine kinase inhibitors.

Aims: To address this issue in a clinical 'real-life' setting, we retrospectively analyzed 45 CP-CML patients (pts) followed in 20 Italian Centers and treated frontline with dasatinib (DAS).

Patients and methods: Median age was 78.4 years (range 75-89.2 years). DAS starting dose was 100 mg QD in 35 pts (77.7%), 80 mg QD in 1 pts (2.2%) and 50 mg QD in 9 pts (20.1%), respectively. The median follow-up was 42.6 months (IQR 20.4 - 63.3).

Results: Grade 3 and 4 side effects, both hematological and non-hematological, were detected in 6 (13.3%) and 12 (26.6%) pts, respectively. Pleural effusions of all grades occurred in 13 pts (28.8%) after a median period of DAS exposure of 14.7 months (IQR 3.0 - 33.1). The rates of DAS dose reduction and permanent drug discontinuation were 53.3% and 20.0%, respectively. As the best response, 42/45 patients (93.3%) achieved a complete cytogenetic response (CCyR), 35/45 (77.7%) a major molecular response (MMR) and 24/45 (53.3%) a deep molecular response (both MR 4.0 and MR 4.5). Only 1 patient (2.2%) progressed to the blast phase after 13 months of therapy; 8 deaths were observed (1 CML-related and 7 CML-unrelated). Cumulative event-free survival and overall survival at 36 months were 64.7% (95%, CI 49.4 - 80.0) and 82.3% (95%, CI 70.3-94.3), respectively.

Conclusion: These findings, although evaluated in a limited and selected cohort of patients, suggest that DAS might be effective in older patients (aged >75 years) affected by CP-CML with acceptable toxicity.

Keywords: CML therapy; Chronic myeloid leukemia; dasatinib; imatinib; nilotinib; older CML patients.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Dasatinib / adverse effects
  • Follow-Up Studies
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Protein Kinase Inhibitors* / adverse effects
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • Imatinib Mesylate
  • Dasatinib