MAINTENANCE THERAPY WITH DASATINIB ADMINISTRATED EVERY OTHER DAY IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA
Author(s): ,
Clémence Loiseau
Affiliations:
Service d'hématologie et oncologie,Centre Hospitalier de Versailles,Le Chesnay,France
,
Marc Spentchian
Affiliations:
Laboratoire d'hématologie,Centre Hospitalier de Versailles,Le Chesnay,France
,
Aude Charbonnier
Affiliations:
Service d'hématologie,Institut Paoli-Calmettes,Marseille,France;French CML group,Bordeaux,France
,
Martine Escoffre-Barbe
Affiliations:
Service d'hématologie,CHU de Rennes,Rennes,France;French CML group,Bordeaux,France
,
Jean Michel Cayuela
Affiliations:
Laboratoire d'Hématologie,Hôpital Saint Louis APHP,Paris,France
,
Sophie Rigaudeau
Affiliations:
Service d'hématologie et oncologie,Centre Hospitalier de Versailles,Le Chesnay,France
,
Lydia Roy
Affiliations:
Service d'hématologie,Hôpital Henri Mondor APHP,Créteil,France;French CML group,Bordeaux,France
,
Emilie Cayssials
Affiliations:
Service d'hématologie,CHU de Poitiers,Poitiers,France;French CML group,Bordeaux,France
,
Martine Gardembas
Affiliations:
Service d'hématologie,CHU d'Angers,Angers,France;French CML group,Bordeaux,France
,
Viviane Dubruille
Affiliations:
Service d'hématologie,CHU de Nantes,Nantes,France;French CML group,Bordeaux,France
,
Jean-Christophe Ianotto
Affiliations:
Service d'hématologie,CHU de Brest,Brest,France
,
Francoise Huguet
Affiliations:
Service d'hématologie,Institut Universitaire du Cancer Toulouse - Oncopôle,Toulouse,France;French CML group,Bordeaux,France
,
Agnes Guerci
Affiliations:
Service d'hématologie,CHU de Nancy,Nancy,France;French CML group,Bordeaux,France
,
Valérie Coiteux
Affiliations:
Service d'hématologie,Hôpital Claude Huriez,Lille,France;French CML group,Bordeaux,France
,
Pascale Cony-Makhoul
Affiliations:
Service d'hématologie,Centre Hospitalier Annecy Genevois,Pringy,France;French CML group,Bordeaux,France
,
François Xavier Mahon
Affiliations:
Institut Bergonié,Bordeaux,France
Philippe Rousselot
Affiliations:
Service d'hématologie et oncologie,Centre Hospitalier de Versailles,Le Chesnay,France;INSERM U1173,Université Versailles-Saint-Quentin-en-Yvelines, Université Paris-Saclay,Saint-Quentin-en-Yvelines,France;French CML group,Bordeaux,France
EHA Library. Loiseau C. Jun 16, 2018; 215435; PS1121
Clemence Loiseau
Clemence Loiseau
Contributions
Abstract

Abstract: PS1121

Type: Poster Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 17:30 - 19:00

Location: Poster area

Background

Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) approved in first and subsequent lines for the treatment of patients (pts) with chronic phase-chronic myeloid leukemia (CP-CML). The standard dosing regimen is once daily resulting in a [C]max associated with a transient inhibition of BCR-ABL kinase activity. In order to optimize tolerability, we proposed a maintenance therapy with dasatinib once every 48h in CP-CML pts in deep molecular response (MR4; BCR-ABLIS≤0.01%).

Aims

We first conducted a retrospective analysis on real-life CML pts allocated to maintenance therapy and then proposed a prospective maintenance study as part of the OPTIM dasatinib trial (EudraCT 2008-006854-17). The primary objective was to assess survival in maintenance without loss of MMR (BCR-ABLIS>0.1%).

Methods

Kaplan-Meier estimates for maintenance without loss of MMR were calculated between two groups of pts in the retrospective cohort (pts in MR4 or pts matching the Euroski eligibility criteria (duration of TKIs ≥3y and duration of MR4≥1y). Pts with duration of TKIs ≥3y and duration of MR4≥1y were eligible for inclusion in the prospective maintenance study. 

Results

Fifty-two CP-CML pts were eligible for the retrospective cohort, after one or two lines of therapy. Thirty-six pts were included in the prospective maintenance study after front line dasatinib.  Median age at diagnosis was 47.8y (range 18.9-78) and 48% pts were male. Median duration of dasatinib in the retrospective cohort and in the prospective study was 40.5 months (range 6.2-116) and 47.7 months (range 32.7-88.4) respectively. Median daily dose before maintenance was 50 mg (range 40-100) and 100 mg (range 40-100) in both retrospective and prospective cohorts respectively. At baseline, 46% of the pts matched the Euroski criteria in the retrospective cohort.

Median follow-up was 28.2 months and 30.7 months in both retrospective and prospective cohorts respectively. Kaplan-Meier estimate of survival without MMR loss in the retrospective cohort was 95.7% (95% CI, 89.9-100) at 12 months and 88.5% (95% CI, 79.4-98.6) at 24 months. We then focused on pts with duration of TKIs≥3y and duration of MR4≥1y. Only one patient lost MMR at 12.2 months. Survival in maintenance without MMR loss was 95% (95% CI, 85-100) at 12 and 24 months. As a comparison, 5 pts lost MMR if only MR4 was achieved at maintenance start. We then analyzed survival in maintenance without loss of MMR in the prospective study. Only 2 pts lost MMR after 23.3 and 36.6 months and maintenance without MMR loss was 100% at 12 months, 95.4% (95% CI, 71.8-99.2) at 24 months. These two pts regained a deep molecular response with dasatinib once daily without occurrence of BCR-ABL tyrosine kinase domain mutation. Focusing on pts included in the prospective study, 5 pts lost MR4 during maintenance at 3.3, 7.7, 8.9, 23.3 and 27.6 months including 2 pts who spontaneously regained MR4 during maintenance continuation and the 2 pts who lost MMR later. Tolerability was excellent with no withdrawal syndrome and no pleural effusion during maintenance.

Conclusion

A maintenance therapy with dasatinib once every 48 hours after achievement of a deep molecular response is feasible. Pts with duration of TKIs≥3y and duration of MR4≥1y experienced very high rates of survival in maintenance without loss of MMR (>95%) and without dasatinib related toxicities. Our results suggest that maintenance with dasatinib is an attractive option for pts in sustained deep molecular response.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Chronic myeloid leukemia, Maintenance, Molecular response, Tyrosine kinase inhibitor

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