Is it possible to reduce the dose of tyrosine kinase inhibitors and maintain response in chronic-phase Philadelphia chromosome– positive chronic myeloid leukemia? A single-center experience.

Abstract

Introduction. Since the introduction of tyrosine kinase inhibitors (TKIs) in 2001, chronic myeloid leukemia (CML) has become a chronic disease, with survival comparable to that of the general population. This entails lifelong treatment and prolonged exposure to long-term toxicities. Although the current goal is treatment discontinuation after achieving sustained deep responses over a defined period, fewer than 50% of patients achieve this outcome, while the remainder require long-term therapy. Therefore, strategies such as dose reduction (DR) are essential to mitigate adverse events (AEs). Prospective evidence remains limited. Materials and Methods: An analytical, retrospective cohort study was conducted. Patients aged ≥18 years with a diagnosis of chronic-phase chronic myeloid leukemia (CML-CP) who required tyrosine kinase inhibitor (TKI) dose reduction (DR) due to adverse events (AEs), intolerance, or other causes were included between 2001 and 2024 at a single center in the City of Buenos Aires. Results: Out of 329 patients with CP-CML, 25 who required TKI dose reduction during treatment were included. Eighty percent (20/25) reduced the dose due to toxicity. In the remaining cases, dose reduction was performed in the context of achieving a major molecular response (MMR) or deeper responses, according to physician judgment. Among the 21 patients who initiated DR with MMR or achieved it during the process, MMR loss-free survival (MMRLFS) at 24 months was 85%, increasing to 94% in the subgroup of 16 patients who had already achieved MMR at the time of DR initiation. In terms of safety, the AEs leading to dose adjustment completely resolved in 17 patients (68%). Discussion: In this study, TKI dose reduction appears to be a safe strategy that maintains response in most patients—particularly in those with prior MMR—and reduces toxicity in the majority of cases. This approach improves quality of life and adherence without compromising efficacy. In cases of response loss, re-escalation to the standard dose generally allows recovery of MMR.