Observational, Retrospective and Multicenter Analysis of Spanish CML Group, in Patients with Chronic Myeloid Leukemia in Treatment-Free Remission after Discontinuation of Bosutinib

INTRODUCTION

Treatment-free remission (TFR) is a goal for the management of chronic myeloid leukemia (CML) when a deep molecular response (DMR) is achieved. This strategy has been evaluated in numerous clinical trials with imatinib, nilotinib or dasatinib. However, none of them have analyzed the feasibility of TFR in CML patients treated with bosutinib. The main objective is to analyze the proportion of patients who maintained a DMR after discontinuation of bosutinib.

METHODS

This is an observational, retrospective, multicenter and real-life study of patients diagnosed with Philadelphia chromosome-positive (Ph+) CML in chronic phase and with whom, according to the European Leukemia Net (ELN) recommendations, a strategy of TFR was chosen after being treated with bosutinib. This data was collected from 12 Spanish Hospitals. As an inclusion criterion, patients had to have achieved a DMR after being treated with bosutinib.

RESULTS

Twenty-three patients from thirteen Spanish centers diagnosed between 1993 and 2017 were included. Among them, 12 were female and 11 male with an average age of 49 years (24-83).

Regarding treatment, no patient received interferon alfa (IFN-α) prior to the initiation of an TKI. Discontinuation of bosutinib was carried out in all 23 patients, the median number of previous lines being 3 (3 patients in 1st line; 4 in 2nd line; 9 in 3rd line; 5 in 4th line; and 2 in 5th line). What motivated the adoption of such a strategy was intolerance to treatment (11 patients) or the presence of a maintained molecular response (MR) ≥ 4.0 (12 patients). Patients maintained bosutinib for a median of 54 (6-83) months before discontinuation.

During follow-up, 7 patients (30,43%) lost TFR after a median of 6 months (2-44), being treated again with bosutinib in 4 patients and with asciminib (new line) in the remaining. All of them achieved DMR again. The remaining 16 patients maintained TFR at the time of data collection with a median of 42 months (2-108). It is important to highlight that the main variable that could be related to the success of discontinuation was the time the patients were treated with bosutinib (24 vs 55 months). No relationship was observed for other variables such as Sokal index, age or number of lines of treatment.

CONCLUSIONS

Our data show that it is possible to opt for a strategy of TFR in patients who have achieved an MMR with bosutinib, being the TFR rate of 69% after a median follow-up of 42 months. These are encouraging data that hint at possible lines of research that could have an impact on the management of CML.

The authors state that they have received funding from Pfizer to conduct this study.

Maortua Langdon:Incyte: Honoraria. De Paz:Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Xicoy:BMS: Honoraria. Martinez Lopez:Pfizer: Honoraria. Perez Lopez:Pfizer: Honoraria. De Las Heras:Pfizer: Honoraria. García Gutiérrez:CTA: Honoraria; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis, Incyte: Speakers Bureau; Novartis, Incyte, GSK, Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy; Novartis BMS Pfizer Incyte GSK: Consultancy.