Author(s): ,
Dietrich Kämpfe
Praxis f. Hämatologie u. Onkologie,Lüdenscheid,Germany
Jörg Brenn
Incyte Biosciences Germany GmbH,Planegg/Martinsried,Germany
Thomas Haverkamp
Leitung Analysenbereich Molekulargenetik II,MVZ Dr. Eberhard & Partner Dortmund (GbR),Dortmund,Germany
Christoph Schulte
Institut für Hämatopathologie Hamburg, Dres. Tiemann, Schulte Holding GmbH,Hamburg,Germany
Hans Tesch
Centrum für Hämatologie und Onkologie Bethanien,Frankfurt / M.,Germany
Harald Stein
Pathodiagnostik Berlin, Berliner Referenzzentrum für Lymphom- und Hämatopathologie,Berlin,Germany
EHA Library. KÄMPFE D. Jun 14, 2018; 216311; PB1952
Dietrich KÄMPFE
Dietrich KÄMPFE

Abstract: PB1952

Type: Publication Only


Treatment-free remission (TFR) is an achievable goal for patients with chronic myeloid leukemia (CML) in the tyrosine kinase inhibitor (TKI) era. Median follow-up time in studies up to 60 month are documented very well, and stable molecular remissions (MR)>3 in approximately 50 % of patients during this period are reported. Treatment conditions differ in primary therapy (type of TKI; IFNa ?) and in duration of deep molecular remission (mostly 1 to 2 years in current studies with 2nd GenTKI)


To enhance the current debate: "How to achieve TFR?" we describe 7 patients of our "real world" register, who are in TFR for at least 2 years after Imatinib (IMA) as their 1st line TKI- therapy.


Our register includes 52 CML-patients, newly diagnosed between 01/1998 and 12/2017. Median age (62,1y, 22 - 84y), sex ratio (m : f = 1,7 : 1) and raw incidence (1,1/105) correspond to literature. Diagnoses are based on morphological and genetic findings of EUTOS-accredited laboratories. Ending the TKI - therapy was considered after 3 years of continuous genetic remission (MR > MR 4,5 and / or nested PCR negativity). 8 of 14 candidates finished therapy that way. 1 more patient finished 6 months after IMA in 2nd molecular remission after previous allo-transplant.


After stopping TKI - therapy 7 of 9 patients (77,8 %) remained in complete molecular remission. Median OS from diagnosis is 187,1 months (119 - 240 mo). Median duration of TFR is 59,5 months (24,5 - 144,5 mo). Median age (at diagnosis) was 56,9 years (40,8 - 69,4 ys), sex ratio (m : f) is 5 : 2. BCR-ABL transcript type E14a2 was found in 4 vs. E13a2 in 2 patients (1x unknown), which may be different from the expected ratio in CML-CP. EUTOS risk was "high" in 3 patients; 1 of 7 was in primary accelerated phase (pAP). 1 patient got TKI after initially aggressive conventional chemotherapy and consecutive HU / IFNα ("OSHO 1995" - study) for 174 months, with interruption of IFNα for 24 months because of autoimmune thyreoiditis. Also 2 other patients received IFNα prior to TKI, 1 in combination ("CML IV" study, later in the "NICOLI" study - immediately finished because of GUILLAIN-BARRE-like-syndrome). TKI was changed from IMA to DASA in 1 and to NILO in another case. Body mass index (BMI) of 2 patients was > 30, 1 of them got IMA mainly 300 mg per day.
Remarkably in 2 patients JAK2 - mutation was detected (low level, but consistently), one in combination with KIT – mutation and one in a patient with splenomegaly and suspected 2nd n
eoplasia (CMML? MDS?) who acquired additional KRAS & CSMD1 mutations in addition to a presumably germline variant of JAK3 (p.V722I). 


Despite limited number of patients our real life experience illustrates:

1.) TFR more than 10 years is an achievable aim, also in patients treated with IMA as a 1st line TKI and under real life conditions. 2.) Most common features of our TFR-patients were: 3-year continuing deep mol.-genetic remission (6/7) and after using IFNα (4/7). Both common features are discussed thoughtfully in the literature. Most other characteristics were heterogeneously. 3.) As recently discussed (GALE and HOCHHAUS 2018) TFR may be achieved by one or in combination of different mechanisms. This could correspond to the heterogeneous characteristics of our patients. 4.) Furthermore TFR stabilizing effect could be growth-inhibition by non-BCR-ABL-mutated subclones implying passenger mutations.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Chronic myeloid leukemia, Interferon alpha, Treatment-free remission, Tyrosine kinase inhibitor

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