Institute of Hematology 'L. & A. Seràgnoli', Department of Experimental, Diagnostic and Specialty Medicine
Contributions
Type: Oral Presentation + travel grant
Presentation during EHA20: From 14.06.2015 08:00 to 14.06.2015 08:15
Location: Room Strauss 1
Background
Imatinib mesylate (IM) has been for many years the standard of care for chronic myeloid leukemia (CML) in early chronic phase (CP). As first-line treatment, IM produce high probability of long-term survival, but few patients are able to achieve a stable deep molecular response (MR4.0 or better), that is a pre-requisite to discontinue the TKI treatment. The treatment-free remission (TFR) is an emerging CML treatment goal. The identification of patients with higher probability of achieving a stable deep molecular response is important for the optimization of treatment strategy.
Aims
The aim of the present study was to investigate the predictors of MR4.0 in CML patients treated frontline with imatinib.
Methods
We analyzed 559 patients enrolled within 3 multicentric prospective studies conducted by the GIMEMA CML WP (NCT00514488, NCT00510926, observational trial CML023). Definitions: major molecular response (MMR), BCR-ABLIS ratio < 0.1%; deep molecular response (MR4.0), detectable disease ≤ 0.01% BCR-ABLIS or undetectable disease with ≥ 10,000 ABL transcripts; stable MR4.0: MR4.0 lasting > 24 months and > 3 evaluable samples; unstable MR4.0: unconfirmed occasional positive samples < 0.1% BCR-ABLIS in patients with a stable MR4.0 (Rousselot et al. J Clin Oncol 2014). The intention-to-treat population of each study was analyzed and all the 559 enrolled patients were included.
Results
Baseline demographics characteristics: median age, 52 years (extremes 18-84 years); male/female sex, 60%/40%; high Sokal, high Euro and high EUTOS scores, 22%, 7% and 7%, respectively; clonal chromosomal abnormalities (CCA) in Ph+ cells, 4% (not evaluable in 32% of patients for insufficient number of metaphases); e13a2 BCR-ABL transcript, 36%. The median follow-up was 82 (60-105) months. The median time to MMR and MR4 was 8 and 42 months, respectively. The rate of MR4.0 at 24, 36, 48 and 60 months was 18%, 27%, 30% and 33%, respectively. Overall, 61% of patients achieved a MR4.0 at least once. According to the previously detailed criteria, at the last contact 28% of patients had a stable MR4.0 and 12% had an unstable MR4.0 (stable + unstable MR4.0 = 40%). The median duration of stable MR4.0 was 36 months and the median duration of stable + unstable MR4.0 was 40 months. In a multivariate Cox analysis including baseline variables, female sex, smaller spleen size and e14a2 transcript type resulted independent good prognostic factors on the probability to achieve a MR4.0. Female sex was the only baseline variable able to predict a stable MR4.0. The reduction of BCR-ABL1 transcript levels and the time to molecular response are influenced by baseline variables, so the impact of the dynamics of molecular response on the probability of MR4.0 was analyzed separately: the time to MMR strongly predicted both the achievement and the stability of MR4.0.
Summary
As suggested by a previous report (Branford et al. Blood 2013), in a large nationwide multicentric experience, the female sex was confirmed as a predictor of the achievement of a stable deep molecular response. Moreover, our results support strategies aimed to a rapid reduction of BCR-ABL1 transcript levels to optimize potential suitability for imatinib discontinuation studies.
Keyword(s): Chronic myeloid leukemia, Imatinib, Molecular response, Prognostic factor
Session topic: CML: Molecular-cytogenetic diagnostics
Type: Oral Presentation + travel grant
Presentation during EHA20: From 14.06.2015 08:00 to 14.06.2015 08:15
Location: Room Strauss 1
Background
Imatinib mesylate (IM) has been for many years the standard of care for chronic myeloid leukemia (CML) in early chronic phase (CP). As first-line treatment, IM produce high probability of long-term survival, but few patients are able to achieve a stable deep molecular response (MR4.0 or better), that is a pre-requisite to discontinue the TKI treatment. The treatment-free remission (TFR) is an emerging CML treatment goal. The identification of patients with higher probability of achieving a stable deep molecular response is important for the optimization of treatment strategy.
Aims
The aim of the present study was to investigate the predictors of MR4.0 in CML patients treated frontline with imatinib.
Methods
We analyzed 559 patients enrolled within 3 multicentric prospective studies conducted by the GIMEMA CML WP (NCT00514488, NCT00510926, observational trial CML023). Definitions: major molecular response (MMR), BCR-ABLIS ratio < 0.1%; deep molecular response (MR4.0), detectable disease ≤ 0.01% BCR-ABLIS or undetectable disease with ≥ 10,000 ABL transcripts; stable MR4.0: MR4.0 lasting > 24 months and > 3 evaluable samples; unstable MR4.0: unconfirmed occasional positive samples < 0.1% BCR-ABLIS in patients with a stable MR4.0 (Rousselot et al. J Clin Oncol 2014). The intention-to-treat population of each study was analyzed and all the 559 enrolled patients were included.
Results
Baseline demographics characteristics: median age, 52 years (extremes 18-84 years); male/female sex, 60%/40%; high Sokal, high Euro and high EUTOS scores, 22%, 7% and 7%, respectively; clonal chromosomal abnormalities (CCA) in Ph+ cells, 4% (not evaluable in 32% of patients for insufficient number of metaphases); e13a2 BCR-ABL transcript, 36%. The median follow-up was 82 (60-105) months. The median time to MMR and MR4 was 8 and 42 months, respectively. The rate of MR4.0 at 24, 36, 48 and 60 months was 18%, 27%, 30% and 33%, respectively. Overall, 61% of patients achieved a MR4.0 at least once. According to the previously detailed criteria, at the last contact 28% of patients had a stable MR4.0 and 12% had an unstable MR4.0 (stable + unstable MR4.0 = 40%). The median duration of stable MR4.0 was 36 months and the median duration of stable + unstable MR4.0 was 40 months. In a multivariate Cox analysis including baseline variables, female sex, smaller spleen size and e14a2 transcript type resulted independent good prognostic factors on the probability to achieve a MR4.0. Female sex was the only baseline variable able to predict a stable MR4.0. The reduction of BCR-ABL1 transcript levels and the time to molecular response are influenced by baseline variables, so the impact of the dynamics of molecular response on the probability of MR4.0 was analyzed separately: the time to MMR strongly predicted both the achievement and the stability of MR4.0.
Summary
As suggested by a previous report (Branford et al. Blood 2013), in a large nationwide multicentric experience, the female sex was confirmed as a predictor of the achievement of a stable deep molecular response. Moreover, our results support strategies aimed to a rapid reduction of BCR-ABL1 transcript levels to optimize potential suitability for imatinib discontinuation studies.
Keyword(s): Chronic myeloid leukemia, Imatinib, Molecular response, Prognostic factor
Session topic: CML: Molecular-cytogenetic diagnostics