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DURABLE TREATMENT-FREE REMISSION (TFR) FOLLOWING FRONTLINE NILOTINIB (NIL) IN PATIENTS (PTS) WITH CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE (CML-CP): ENESTFREEDOM 96-WK UPDATE
Author(s): ,
David Ross
Affiliations:
SA Pathology,Adelaide,Australia
,
Tamas Masszi
Affiliations:
Department of Haematology and Stem Cell Transplantation,St István and St László Hospital,Budapest,Hungary
,
María Teresa Gómez Casares
Affiliations:
Hospital Universitario Doctor Negrin,Las Palmas de Gran Canaria,Spain
,
Andrzej Hellmann
Affiliations:
Medical University of Gdańsk,Gdańsk,Poland
,
Jesper Stentoft
Affiliations:
Aarhus University Hospital,Aarhus,Denmark
,
Eibhlin Conneally
Affiliations:
St James Hospital,Dublin,Ireland
,
Valentin Garcia Gutierrez
Affiliations:
Hospital Ramon Y Cajal,Madrid,Spain
,
Norbert Gattermann
Affiliations:
Universitätsklinikum Düsseldorf,Düsseldorf,Germany
,
Philipp le Coutre
Affiliations:
Charité - Universitätsmedizin Berlin,Berlin,Germany
,
Bruno Martino
Affiliations:
Azienda Ospedaliera Bianchi Melacrino Morelli,Reggio Calabria,Italy
,
Susanne Saussele
Affiliations:
III. Med. Klinik,Medizinische Fakultät Mannheim der Universität Heidelberg,Mannheim,Germany
,
Francis Giles
Affiliations:
NMDTI,Robert H. Lurie Comprehensive Cancer Center of Northwestern University,Chicago,United States
,
Jerald Radich
Affiliations:
Clinical Research Division,Fred Hutchinson Cancer Research Center,Seattle,United States
,
Giuseppe Saglio
Affiliations:
University of Turin,Orbassano,Italy
,
Prashanth Gopalakrishna
Affiliations:
Novartis Pharma AG,Basel,Switzerland
,
Weiping Deng
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Nancy Krunic
Affiliations:
Novartis Institute for Biomedical Research,Cambridge,United States
,
Veronique Bedoucha
Affiliations:
Novartis Pharma AG,Basel,Switzerland
Andreas Hochhaus
Affiliations:
Abteilung Hämatologie/Onkologie,Universitätsklinikum Jena,Jena,Germany
EHA Library. Ross D.
Jun 24, 2017; 181888
Dr. David Ross
Dr. David Ross
Contributions
Abstract

Abstract: P601

Type: Poster Presentation

Presentation during EHA22: On Saturday, June 24, 2017 from 17:30 - 19:00

Location: Poster area (Hall 7)

Background
ENESTfreedom (NCT01784068) is evaluating the ability to stop NIL and remain in TFR in pts with a sustained deep molecular response (DMR) on frontline NIL. Previous results from ENESTfreedom showed that 51.6% of pts (98/190) who attempted TFR remained off treatment and in major MR (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [IS]) at 48 wk.

Aims
To analyze updated TFR data and predictive factors for remaining in TFR in ENESTfreedom.

Methods
Eligible pts had CML-CP with b2a2 and/or b3a2 BCR-ABL1 transcripts, ≥ 2 y of frontline NIL, and MR4.5 (BCR-ABL1IS ≤ 0.0032%) prior to enrollment. All pts provided informed consent. After enrollment, pts continued NIL for 1 y (consolidation phase). MR was assessed every 12 wk during the 1-y consolidation phase; pts with no assessment worse than MR4 (BCR-ABL1IS ≤ 0.01%), ≤ 2 assessments between MR4 and MR4.5, and MR4.5 in the last assessment were eligible to enter TFR. Loss of MMR during TFR triggered reinitiation of NIL. To investigate potential predictors for remaining in TFR, pts were grouped according to Sokal risk score at diagnosis or depth of response prior to attempting TFR (based on response assessments in the consolidation phase), and 48-wk TFR rates in each subset were calculated. The current analysis was conducted when all pts who entered TFR had completed 96 wk of TFR, reinitiated NIL, or discontinued from the study (data cutoff, 31 Oct 2016).

Results
Of 190 pts who entered TFR, 93 (48.9% [95% CI, 41.6% - 56.3%]) remained in MMR and off treatment at wk 96, including 88 (46.3%) who were in MR4.5. Three pts who were in TFR at 48 wk lost MMR by 96 wk, and 2 additional pts discontinued from the study between 48 and 96 wk without losing MMR. Among pts with low, intermediate, or high Sokal risk at diagnosis, 39/62 (62.9% [95% CI, 49.7% - 74.8%]), 25/50 (50.0% [95% CI, 35.5% - 64.5%]), and 9/28 (32.1% [95% CI, 15.9% - 52.4%]), respectively, remained in TFR at wk 48 (Sokal risk scores were missing for 50 pts). Among pts with MR4.5 in all assessments during the consolidation phase, 90/170 (52.9% [95% CI, 45.2% - 60.6%]) remained in TFR at wk 48 vs 8/20 (40.0% [95% CI, 19.1% - 63.9%]) who had ≥ 1 assessment between MR4 and MR4.5 during the consolidation phase. Overall, of 88 pts who reinitiated NIL due to loss of MMR, 87 (98.9%) regained MMR and the remaining pt left the study 7.1 wk after NIL reinitiation without regaining MMR; 81 of 88 pts (92.0%) regained MR4.5 by the data cutoff. Among pts remaining in TFR for > 48 wk (n = 100), adverse events (AEs) were less frequent during the second vs the first 48 wk of TFR; 2 (2.0%) and 1 (1.0%) of these pts had cardiovascular AEs during the first and second 48 wk of TFR, respectively; 34 (34.0%) and 9 (9.0%), respectively, had AEs in the predefined musculoskeletal pain grouping.

Conclusion
The majority of pts in TFR at 48 wk remained in TFR at 96 wk, and they reported fewer AEs during the second 48 wk of TFR than in the first 48 wk, affirming the durability and safety of TFR following NIL. No strong predictors for remaining in TFR were identified. Pts with low Sokal risk and pts with continuous MR4.5 in the consolidation phase tended to have higher TFR rates than other pts, although these results must be interpreted with caution due to the small number of pts in some subsets and the wide 95% CIs. Additionally, the biological explanation for an association between Sokal risk score at diagnosis and a subsequent ability to remain in TFR is unknown. These results support TFR as a valuable option for pts in sustained DMR on frontline NIL.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Clinical Trial, Chronic myeloid leukemia

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