Determination of the Percentage of CML Patients that Achieve Continuous Complete Molecular Response Under Treatment with TKIs and Are Eligible for Participation in a TKI Discontinuation Study
Authors: Georgiou George , Roumelioti Maria , Dimou Maria , Palaiologou Danai , Stefanou Angeliki , Staikou Efstathia , Kyrtsonis Marie-Christine , Angelopoulou Maria K. , Vassilakopoulos Theodoros P. , Galani Zacharoula I , Plata Eleni , Variami Eleni , Korantzis Ioannis , Tsatalas Konstantinos , Protopapa Maria , Papaioannou Maria , Pangalis Gerasimos , Marinakis Theodore , Xanthopoulidis Georgios , Pappi Vassiliki , Vervesou Elissavet , Symeonidis Argiris , Matsouka Charis , Anargyrou Konstantinos , Tsionos Konstantinos , Vyniou Nora , Gougopoulou Dimitra , Liapi Dimitra , Kolokythopoulos Dionysis , Roussou Paraskevi , Reppa Konstantina , Poumbouridou Eleni , Katodritou Eirini , Klonizakis Ioannis , Panayiotidis Panayiotis 
Published: October 2019

Abstract
Abstract 4446
First-line therapy for Chronic Myeloid Leukemia (CML) is based on the tyrosine kinase inhibitor Imatinib, according to the published recommendations of the European Leukemia Net (Baccarani et al, JCO, 2009). CML patients that achieve the goals of treatment, remain under imatinib therapy for life, according to the ELN recommendations. Many CML patients treated for 5–10 years with imatinib ask about the possibility of stopping or reducing their treatment and poor imatinib adherence is observed in this group of CML patients. In the clinical trial STIM (STop IMatinib), Mahon FX et al., Lancet 2010,), 41% of 100 selected CML patients treated with imatinib that had achieved “complete molecular response” (CMR) for >2 years remained in CMR one year after discontinuation of Imatinib treatment. In patients with molecular relapse, re-introduction of imatinib resulted in molecular responses or CMR. This study demonstrated that a subpopulation of CML patients in CMR may discontinue safely imatinib. However the percentage of CML patients achieving CMR/ continuous CMR differs in published clinical trials and the definition of CMR is different between CML groups, since no standarization is currently available. Moreover, the actual percentage of CML patients that achieve CMR under TKI treatment in the every day clinical practice, outside of clinical trials (were several exlusion criteria exist), is not well defined. In the European trial Stop Kinase Inhibitors (EURO-SKI), it is planned to discontinue TKIs from CML patients that have received TKIs > 3 years and have CMR (according to EUTOS guidelines) for a minimum of 1 year. The aim of this study was to identify the percentage of CML patients treated with TKIs in the every day clinical practice, that meet the proposed EURO-SKI criteria.CMR was determined using the current definitions of EUTOS for CML for the determination of CMR: CMR4 (or molecular response MR4), when in a RQ-PCR, BCR-ABL1 transcripts are undetectable and the number of copies of the control abl gene are >10,000 and CMR 4,5 (or MR 4,5) when the number of the abl copies are > 32,000. In our Center, we monitor BCR-ABL1 levels in 510 CML patients treated with TKIs in 42 medical centers in Greece. Median age at diagnosis of CML is 58 years, 50.5% are females and median follow-up time 3.5 years. RQ-PCR is performed with the FusionQuant®Kit BCR-ABL (IPSOGEN,) where ABL1 is used as the internal control gene.

Results:
at the time of analysis 52 out of 510 CML patients (10.2%) were found to have CMR in at least 3 consecutive RQ-PCR assays during a period of at least 12 months and had received TKI therapy for at least 3 years; 41 out these 52 CML patients were in MR4 and 11 were in MR4.5.

Conclusions:
In an unselected population of CML patients, treated in routine clinical practice, 52 out of 510 (10.2%) achieved continuous CMR according to EUTOS guidelines and can be eligible to participate in TKI discontinuation studies.

Disclosures:
No relevant conflicts of interest to declare.