PS1192 INITIAL REPORT OF A NILOTINIB DISCONTINUATION PROJECT WITH 54 GREEK CML PATIENTS FOLLOWED IN ACCORDANCE TO THE APPROVED DISCONTINUATION INDICATION OF THE DRUG
Authors: Dimou M. , Roumelioti M. , Touloumenidou T. , Stefanou A. , Staikou E. , Iliakis T. , Angelopoulou M. , Kouraklis A. , Symeonidis A. , Adamopoulos I. , Papalexandri A. , Panayiotidis P. 
Published: June 2019

Background:

Discontinuation of Tyrosine Kinase Inhibitors treatment in chronic phase(CP) chronic myeloid leukemia(CML) patients(pts) has become a new treatment goal and many emerging data shows that it can be feasible in a considerable number of pts, if some criteria are fulfilled [CP disease, adequate time of TKI treatment and deep molecular remission, stringent follow up with quantitative bcr‐abl RT‐PCR (IS)].

ENESTop and ENESTFreedom are two phase 2 trials, which evaluated the percentage of CP CML pts that can be treatment free after Nilotinib(NL) discontinuation at Week 48 (patients at least 3 years on NL and at least 1 year in MR4,5). Given this outcome (57,9% and 51,6% accordingly‐primary endpoint fulfilled), EMEA permitted the addition of discontinuation of NL to the summary of product characteristics of the drug (SmPC) in June 2017.

Aims:

We will present the preliminary data of NL discontinuation in 54 Greek CP CML pts, followed according to the approved discontinuation indication of the drug.

Methods:

Pts with CP CML that have received NL 300 mg BID either as 1st or subsequent line (not for resistance) for at least 3 years and have confirmed MR4,5 for at least 1 year, discontinue treatment, according to the approved discontinuation indication of the drug. After discontinuation, they are followed with qRT‐PCR (in 2 Greek MR4,5 EUTOS certified labs), monthly for the 1st year, every 6 weeks for the 2nd year and every 3 months thereafter. In case of relapse, which is defined as MMR loss, pts restart immediately treatment and are followed monthly until MMR reachievement and then every 3 months. This NL discontinuation project is sponsored by the Hellenic Society of Hematology.

Results:

Between 7/2017 and 1/2019, 54 adult CP CML pts discontinued NL. Patients’ characteristics are shown in table 1. After a median follow up(FU) of 9 months(1–18), 12 pts(22,2%) lost MMR in a median time of 3 months(2–6). No relapse was noticed after the 6th month of FU. The Treatment Free Survival(TFS) for the 6th and 9th month of FU is 77,8% (picture 1). All relapsed pts restarted NL (except 1 who started interferon due to pregnancy). Ten of them regained MMR after 3,5 months(1–5), 8 pts regained MR4 after 4 months(3–8) and 3 pts (including the pregnant pt) regained MR4,5 after 6 months(6–9). No accelerated or blastic phase was observed. During this discontinuation period there was a saving of 837.000 Euros for the Greek Health Care System.

Summary/Conclusion:

Despite the limited FU period, our data from 54 CP CML pts who discontinued NL according to the approved indication of the drug compare favorably to published data from NL discontinuation studies (Mahon F, et al. ASCO 2018, Radich J, et al. ASCO 2018). Longer duration of NL treatment before discontinuation (our project: 6 years, ENESTop: 4,4 years, ENESTFreedom: 3,6 years) is apparently the main reason of this difference. Longer duration of Imatinib treatment correlated with higher TFS in the Imatinib discontinuation study, EUROSKI (Saussele S, et al. Lancet Oncol 2018), as well. The enrollment and FU of eligible patients (based on the approved indication of the drug) in this NL discontinuation project is ongoing.

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