LONG-TERM TREATMENT-FREE REMISSION (TFR) IN PATIENTS (PTS) WITH CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE (CML-CP) FOLLOWING FRONTLINE (1L) NILOTINIB (NIL): RESULTS FROM ENESTFREEDOM
Author(s): ,
Giuseppe Saglio
Affiliations:
University of Turin,Orbassano,Italy
,
Tamas Masszi
Affiliations:
Semmelweis University,Budapest,Hungary
,
María Teresa Gómez Casares
Affiliations:
Hospital Universitario de Gran Canaria Dr Negrín,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’s Hospital,Dublin,Ireland
,
Valentin Garcia Gutierrez
Affiliations:
Hospital Universitario Ramón y Cajal, IRYCIS,Madrid,Spain
,
Norbert Gattermann
Affiliations:
Universitätsklinikum Düsseldorf,Düsseldorf,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
,
Phillipp le Coutre
Affiliations:
Charité - Universitätsmedizin Berlin,Berlin,Germany
,
Francis J. Giles
Affiliations:
Developmental Therapeutics Consortium,Chicago,United States
,
David M. Ross
Affiliations:
SA Pathology,Adelaide,Australia
,
Jerald P. Radich
Affiliations:
Clinical Research Division, Fred Hutchinson Cancer Research Center,Seattle,United States
,
Manu Sondhi
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Suddhasatta Acharyya
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Shalini Chaturvedi
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Véronique Bédoucha
Affiliations:
Novartis Pharma AG,Basel,Switzerland
Andreas Hochhaus
Affiliations:
Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena,Jena,Germany
EHA Library. Saglio G. Jun 15, 2018; 214841; PF368
Prof. Giuseppe Saglio
Prof. Giuseppe Saglio
Contributions
Abstract

Abstract: PF368

Type: Poster Presentation

Presentation during EHA23: On Friday, June 15, 2018 from 17:30 - 19:00

Location: Poster area

Background
ENESTfreedom (NCT01784068) is the first dedicated study evaluating pts with sustained deep molecular response (DMR) on 1L NIL for achievement of TFR, a new treatment goal in CML. Previous results from ENESTnd showed that more pts achieved sustained DMR (per ENESTfreedom criteria) by 6 y with 1L NIL (37.9% [300 mg BID]) vs 1L imatinib (IM; 21.6%), suggesting that more newly diagnosed pts may reach TFR eligibility with NIL.

Aims
In ENESTfreedom, TFR rates of 51.6% at 48 wk and 48.9% at 96 wk have been reported; here we present a long-term (144-wk) analysis of the durability and safety of TFR.

Methods
Pts with ≥2 y of 1L NIL who achieved MR4.5 (BCR-ABL1 ≤0.0032% on the International Scale [BCR-ABL1IS]) entered a 1-y NIL consolidation phase; those with sustained DMR could enter the main TFR phase. Pts not eligible to enter the main TFR phase received another 1 y of NIL and, if sustained DMR was achieved, they could enter the TFR-2 phase. Pts in either TFR phase restarted NIL after loss of major molecular response (MMR; BCR-ABL1IS ≤0.1%). Data cutoff was Oct 11, 2017, by which all pts who entered the main TFR phase had completed ≥144 wk of TFR, restarted NIL, or discontinued the study. All pts gave informed consent.

Results
At the data cutoff, 89/190 pts in the main TFR phase remained in TFR (46.8%; 95% CI, 39.6%>54.2%); 94 pts (49.5%) lost MMR (91 restarted NIL) and 7 (3.7%) discontinued TFR for other reasons. Only 4/93 pts in TFR at 96 wk were no longer in TFR at 144 wk; 3 of these first lost MR4.5 within the first 8 wk of TFR. Of 91 pts who restarted NIL, 90 (98.9%) regained MMR and 84 (92.3%) regained MR4.5 (1 discontinued study without MMR, 5 discontinued with MMR but not MR4.5, 1 remained in reinitiation phase with MMR but not MR4.5). Of 84 pts who regained MR4.5, 70 (83.3%) had stable MR4.5 48 wk later, 11 (13.1%) discontinued the study <48 wk after regaining MR4.5, and 3 (3.6%) remained on NIL with <48 wk of follow-up after regaining MR4.5.

At the data cutoff, 5/10 pts (50%) who entered the TFR-2 phase remained in that phase; the other 5 lost MMR and restarted NIL (4 regained MR4.5, 1 regained MR4). TFR rate among these 10 pts was 40% at both 48 wk (1 pt had missing 48-wk data) and 96 wk (1 pt had <96 wk of follow-up). Including all pts who attempted TFR (after 1 or 2 y of consolidation), the overall TFR rate was 51% (102/200) at 48 wk and 48.5% (97/200) at 96 wk.

No pt had disease progression. There were 10 deaths: 2 during consolidation (1 cardiac arrest, 1 suicide), 1 during TFR (unknown cause), 4 during reinitiation (1 acute myocardial infarction, 1 respiratory failure, 1 hepatobiliary cancer, 1 unknown cause), 3 >30 d after discontinuing study in the TFR phase (1 mesothelioma) or reinitiation phase (1 transitional cell cancer of renal pelvis and ureter, 1 unknown cause). 144-wk treatment-free survival (TFS) rate (based on main TFR phase) was 48.7% (95% CI, 41.4%>55.6%; Fig.1). Among 94 pts remaining in TFR for >96 wk, any-grade AE rates were 85.1%, 76.6%, 69.1%, and 45.7% in consolidation and the first, second, and third 48 wk of TFR, respectively; any-grade musculoskeletal pain–related AE rates were 16.0%, 40.4%, 9.6%, and 4.3%. Cardiovascular event rates were low across these periods.

Conclusion
These results support the long-term durability and safety of TFR following 1L NIL, with no disease progressions or deaths attributable to CML. Together with ENESTnd data showing higher sustained DMR rates with 1L NIL vs IM, these findings suggest more pts may be able to attempt and achieve TFR with 1L NIL.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Chronic myeloid leukemia, Clinical Trial, Nilotinib, Treatment-free remission

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