Frequency of Complete Molecular Response In Chronic Myeloid Leukemia Patients In Real Life Practice.
Authors: Decamp Matthieu , Istasi Dina , Johnsonansah Atchroue , Reman Oumedaly , Levaltier Xavier , Fruchart Christophe , Launay Vincent , Kadi Seyeffedine , Troussard Xavier 
Published: October 2019

Abstract
Abstract 1227

Introduction:
Scarce data are available on the frequency of complete molecular response (CMR) in chronic myeloid leukemia (CML) patients. The European Leukemia Net defined CMR lately as an undetectable transcript quantified by Real Time PCR and/or nested PCR in two consecutive blood samples of adequate quality, using strict sensitivity criteria (sensitivity > 10 4). CMR is the best response that we can achieve in CML patients. Generally it is obtained after hematopoietic stem cell transplantation (HSCT) but since the administration of tyrosine kinase inhibitors (TKI), the number of patients seen with CMR is continuously increasing. The aim of this study is to assess the frequency of CMR in CML patients, and study their characteristics.

Methods:
A retrospective study was conducted to collect epidemiological, clinical, therapeutic and laboratory data of CML patients followed in hospitals of the region of Basse Normandie in France. All CML patients who had been followed up, between 1999 and 2010, by molecular monitoring for their Bcr-Abl transcript level were included. Clinical and biological responses were defined according to the ELN 2009 recommendations.

Results:
199 patients were included in this study, 154 were diagnosed during the study period. Median age at diagnosis was 54 years and 46% were females. 61.3% were diagnosed in the chronic phase while the accelerated and the blast crisis phase accounted for 10.5% and 0.02%. Among these patients, 2 had the p190 BCR-ABL transcript and 2 the p230 transcript type. 169 were still followed at the end of this study and the median follow up duration was 6,4 years. Out of these 199 patients 12 died and 18 were lost out of sight. Imatinb (IM) alone or Imatinib-based combined therapies in clinical trials, was administrated as a first line treatment in 51,2% of patients. Interferon (INF) alone or in association with other chemotherapy was the frontline therapy in 37,7%; 52% of them started IFN treatment before 2000 and 73% switched to IM. At the time of analysis 26.6% of patients achieved a complete molecular response and 39.7% obtained a major molecular response (MMR) as defined by the international scale; this figure is to be tempered by the fact that the follow up duration was less than 18 months for 9,5% of patients. CMR was obtained in 11 patients following HSCT. With IM as a first line therapy, 11 patients achieved CMR or had an undetectable transcript after a median duration of 43.3 months and lasted for 13.3 months. When IM was given as a second line therapy, 17 obtained a CMR or had an undetectable transcript, in this case the median time calculated starting from the second line treatment administration was 37,3 months and in half of them, it persisted for 28 months. Among these patients, two discontinued therapy and currently they are still on CMR, 24 and 18 months after IM arrest. There was no significant difference in the median CMR achievement duration between the first and second line IM therapy groups. CMR following IFN treatment had been observed in 8 patients, 7 of them stopped IFN and have been in CMR for more than 5 years since its discontinuation. Finally five patients achieved a CMR after administration of second generation TKI. Altogether, a total of 63 patients were followed up for undetectable BCR-ABL transcript. In 53, the transcript remained undetectable; whereas 10 had lost that level of molecular response; 7 of them had regressed to a MMR though they were under IM therapy; 2 lost the MMR, one of them after IM arrest and one progressed to acute leukemia.

Conclusion:
A significant proportion of patients is in CMR or at least had no detectable transcript. In case of TKI therapy, the response is obtained after continuous administration (median duration was 36 months) and is durable in most cases. In this study, few patients in CMR have discontinued treatment but maintained their CMR response. Unfortunately one stopped the treatment and relapsed rapidly. The maintenance of this level of response appears to be dependent on continued suppression of the Bcr-Abl clone by TKI.

Disclosures:
No relevant conflicts of interest to declare.