Dasatinib plus Peg-Interferon alpha 2b combination in newly diagnosed chronic phase chronic myeloid leukaemia: Results of a multicenter phase 2 study (DASA-PegIFN study)

Br J Haematol. 2023 Jan;200(2):175-186. doi: 10.1111/bjh.18486. Epub 2022 Oct 10.

Abstract

Superior rates of deep molecular response (DMR) have been reported with the combination of tyrosine kinase inhibitors and pegylated-interferon-alpha (Peg-IFN) in patients with newly diagnosed chronic phase-chronic myeloid leukaemia (CP-CML). In this setting, this study investigated the efficacy and safety of dasatinib combined to Peg-IFN-α2b (Dasa-PegIFN, NCT01872442). A total of 79 patients (age ≤65 years) started dasatinib; 61 were eligible for Peg-IFNα-2b add-on therapy at month 3 for a maximum 21-months duration. Dasatinib was continued thereafter. The primary endpoint was the cumulative rate of molecular response 4.5 log (MR4.5 ) by 12 months. The results are reported for the 5-year duration of the study. Grade 3 neutropenia was frequent with the combination but did not induce severe infection (one of grade 3). Other adverse events were generally low grade (4% of grade 3-4) and expected. Seventy-nine per cent and 61% of patients continued the Peg-IFN until months 12 and 24, respectively. Overall, at these time points, MR4.5 rates were 25% and 38%, respectively. Thereafter, 32% and 46% of patients achieved a sustained (≥2 years) MR4.5 or MR4 , respectively. This work established the feasibility and high rates of achievement of early and sustained DMR (a prerequisite for treatment-free-remission) with dasatinib and Peg-IFNα-2b combination as initial therapy.

Keywords: chronic myeloid leukaemia; clinical trial; deep molecular response; pegylated-interferon; tyrosine kinase inhibitor.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Dasatinib / adverse effects
  • Humans
  • Interferon-alpha* / adverse effects
  • Leukemia, Myeloid, Chronic-Phase* / drug therapy
  • Polyethylene Glycols / adverse effects
  • Treatment Outcome

Substances

  • Dasatinib
  • peginterferon alfa-2b
  • diazobenzenesulfonic acid
  • Interferon-alpha
  • Polyethylene Glycols

Associated data

  • ClinicalTrials.gov/NCT01872442