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DURABLE TREATMENT-FREE REMISSION (TFR) AFTER STOPPING SECOND-LINE NILOTINIB (NIL) IN PATIENTS (PTS) WITH CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE (CML-CP): ENESTOP 96-WK UPDATE
Author(s): ,
Timothy Hughes
Affiliations:
SA Pathology and South Australian Health and Medical Research Institute, University of Adelaide,Adelaide,Australia
,
Carla Boquimpani
Affiliations:
Hemocentro do Rio de Janeiro - HEMORIO,Rio de Janeiro,Brazil
,
Naoto Takahashi
Affiliations:
Department of Hematology,Akita University Hospital,Akita,Japan
,
Noam Benyamini
Affiliations:
Rambam Health Care Campus,Haifa,Israel
,
Nelma Cristina Clementino
Affiliations:
Hospital Das Clinícas da UFMG,Belo Horizonte,Brazil
,
Vasily Shuvaev
Affiliations:
Russian Research Institute of Hematology and Transfusiology,Saint Petersburg,Russian Federation
,
Sikander Ailawadhi
Affiliations:
Mayo Clinic,Jacksonville,United States
,
Jeffrey Lipton
Affiliations:
Princess Margaret Cancer Centre, University of Toronto,Toronto,Canada
,
Anna Turkina
Affiliations:
National Research Center for Hematology,Moscow,Russian Federation
,
Raquel de Paz
Affiliations:
University Hospital La Paz,Madrid,Spain
,
Beatriz Moiraghi
Affiliations:
Hospital General De Agudos J. M. Ramos Mejia,Buenos Aires,Argentina
,
Franck Nicolini
Affiliations:
Centre Hospitalier Lyon Sud,Pierre Bénite,France
,
Jolanta Dengler
Affiliations:
Onkologische Praxis Heilbronn,Heilbronn,Germany
,
Tomasz Sacha
Affiliations:
Department of Hematology,Jagiellonian University Hospital,Kraków,Poland
,
Dong-Wook Kim
Affiliations:
Seoul St Mary's Hospital, The Catholic University of Korea,Seoul,Korea, Republic Of
,
Rafik Fellague-Chebra
Affiliations:
Novartis Pharma S.A.S.,Rueil-Malmaison,France
,
Sandip Acharya
Affiliations:
Novartis Healthcare Pvt Ltd,Hyderabad,India
,
Nancy Krunic
Affiliations:
Novartis Institutes for Biomedical Research,Cambridge,United States
,
Yu Jin
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
François-Xavier Mahon
Affiliations:
Cancer Center of Bordeaux, Institut Bergonié, INSERM U1218, University of Bordeaux,Bordeaux,France
EHA Library. Hughes T.
Jun 23, 2017; 181544
Timothy Hughes
Timothy Hughes
Contributions
Abstract

Abstract: P257

Type: Poster Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 17:15 - 18:45

Location: Poster area (Hall 7)

Background
ENESTop (NCT01698905) is evaluating the ability to stop treatment and remain in TFR in pts with CML-CP who achieved a sustained deep molecular response (MR) after switching from imatinib (IM) to NIL. In the primary analysis, 57.9% of pts (73/126) who stopped treatment remained in TFR (no loss of major MR [MMR; BCR-ABL1 ≤0.1% on the International Scale (IS)], no confirmed loss of MR4 [BCR-ABL1IS ≤0.01%], and no treatment reinitiation) at 48 wk.

Aims
To evaluate the proportion of pts remaining in TFR at 96 wk after stopping second-line NIL in ENESTop.

Methods
Eligible pts had ≥3 y of prior tyrosine kinase inhibitor treatment (>4 wk IM, then ≥2 y NIL) and achieved MR4.5 (BCR-ABL1IS ≤0.0032%) after switching to NIL. All pts provided informed consent. Enrolled pts continued NIL for 1 y in the consolidation phase (MR assessed every 12 wk). Pts without confirmed loss of MR4.5 during consolidation were eligible to enter the TFR phase (MR assessed every 4 wk for the first 48 wk, every 6 wk for the second 48 wk, then every 12 wk). Pts with loss of MMR or confirmed loss of MR4 reinitiated NIL. This analysis was conducted when all pts who entered the TFR phase had completed 96 wk of TFR, reinitiated treatment, or discontinued from the study (data cutoff, 7 Nov 2016).

Results
At 96 wk of the TFR phase, 67 of the 126 pts (53.2% [95% CI, 44.1% - 62.1%]) who entered the TFR phase remained in TFR. Four pts who were in TFR at 48 wk reinitiated NIL due to confirmed loss of MR4 at 60, 72, 90, and 96 wk, respectively. Two other pts discontinued from the study between 48 and 96 wk due to pregnancy (last BCR-ABL1IS of 0.0035% at 60 wk) and pt decision (maintained MR4.5 through 90 wk), respectively. Based on Kaplan-Meier analysis, the median duration of treatment-free survival has not been reached and the curve appeared to plateau (Figure). Of 56 pts who reinitiated NIL by the data cutoff, 52 (92.9%) regained MR4 and MR4.5, and the time by which 50% regained MR4 and MR4.5 was 12.0 and 13.1 wk, respectively. The time by which 50% of pts regained MR4.5 was shorter for pts who reinitiated NIL due to confirmed loss of MR4 (n=22; 11.0 wk) vs loss of MMR (n=34; 16.0 wk). Two of the 4 re-treated pts who did not regain MR4 were ongoing in the treatment reinitiation phase (duration, 87.9 and 6.9 wk, respectively); the other 2 discontinued from the study before 48 wk, 1 due to not regaining MMR (retreatment duration, 20 wk) and 1 due to an adverse event (AE) after regaining MMR. Two deaths occurred after the first 48 wk of TFR, both in post-treatment follow-up: 1 due to cardiopulmonary failure 111 days after pt discontinued retreatment due to an AE, and 1 due to adenocarcinoma 77 days after pt discontinued retreatment due to initiation of chemotherapy for secondary malignancy. Among pts who remained in TFR for >48 wk (n=73), rates of all-grade AEs were 82.2% and 63.0% during the first and second 48 wk of TFR, respectively, vs 79.5% during the consolidation phase. Rates of musculoskeletal pain-related AEs were 47.9% and 15.1% during the first and second 48 wk of TFR, respectively, vs 13.7% during the consolidation phase.

Conclusion
Updated 96-wk analyses from ENESTop showed stability of the TFR rate, with few pts reinitiating treatment between 48 and 96 wk after stopping second-line NIL. Rates of overall and musculoskeletal pain-related AEs decreased in the second 48 wk of TFR vs the first 48 wk. Overall, these results demonstrate the durability of TFR after stopping NIL in pts who achieved a sustained deep MR after switching from IM to NIL.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Clinical Trial, Chronic myeloid leukemia

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