Only Time Before the Beginning of Treatment and Time to Achieve CCyR Influence the Stability of CCyR In CML-CP Patients On Imatinib Therapy.
Authors: Abdulkadyrov Kudrat , Lomaia Elza , Abdulkadyrova Alla , Udalieva Vera , Shikhbabaeva Dgariyat , Usacheva Elena , Zotova Irina , Machulaitene Elena , Ivanova Maria , Poznyak Ekaterina , Koryagina Elena , Ilina Natalia , Shneider Tatiana , Stepanova Svetlana , Romanova Ekaterina , Salamatova Evgenia , Lazorko Natalia , Martynkevich Irina , Shuvaev Vasiliy , Zaritskey Andrey 
Published: October 2019

Abstract
Abstract 4476
At present, the main goal of chronic myeloid leukemia (CML) therapy is to obtain complete cytogenetic response (CCyR) which is strongly associated with patient's survival. The second main factor for good prognosis after CCyR achievement is its stability. The aim of this study was to reveal factors, influencing the stability of CCyR in CML chronic phase (CML-CP) patients on Imatinib (IM) therapy in routine clinical practice.
Patients and methods: In patients database of St-Petersburg and Leningrad region there are 235 CML-CP patients, who received IM for 12 months or more. Eligibility criteria for analysis were as follow: IM start dosage 400 mg/day, CCyR, which was confirmed by at least 2 consecutive cytogenetic analysis with 0% Ph+ cells in at least 20 metaphases. Patients in CCyR with IM therapy interruptions more than 3 months were censored at the date of last cytogenetic analysis.
Results: 115 patients from our database were found to eligible for analysis. The median age at the diagnosis was 48 years (16-76 years). Male/female ratio was 50/65. The median time from diagnosis to IM treatment was 7 months (0.1-108 months), 55 patients begun the IM treatment in early CML-CP (≤ 6 months since diagnosis). 64, 38 and 13 patients had low, intermediate and high Sokal scores respectively. There were no differences between patients in early and late CML-CP. 56 (48,7%) patients before IM were treated with interferon. The median observation time on IM treatment was 56 months (16-88 months). Overall estimated probability of CCyR loss was 16%, rate 12.1% (14/115). In 10 patients CCyR was lost within major CyR.
The estimated overall survival (all causes of death) was 78% (death rate 4.3% (5/115)), and only 1 death was CML-related.
The probability of CCyR loss was not depend on previous interferon therapy and was equal in both groups -16%. The rate of CCyR loss was 15.3% (9/59) vs 8.9% (5/56) in pts with or without interferon pretreatment respectively. Sokal scores also didn't influence CCyR stability: CCyR loss rates were 10.9% (7/64), 13.2% (5/38), 15.4% (2/13) for low, intermediate and high risks, respectively (p>0.1). Probabilities of CCyR loss in different ages groups were similar: 13% (rate 8% (4/50)) vs 18% (rate 15.4% (10/65)) in patients older and younger than 50 years old, respectively (p>0.1).
CCyR loss was less frequent in early CML-CP 10% (rate 3.6% (2/55)) then in late CML-CP 21% (20% (12/60)), p=0.032. For more thoroughly analysis, patients in late CML-CP were divided in subgroups related to duration of CML before IM initiation: >6 and ≤12 months, >12 and ≤60 and more than 60 months. Probabilities of CCyR loss in this groups were 22% (rate 20% (3/15)), 27% (rate 25.7% (9/35)) and 0% (rate 0% (0/10)), respectively (p<0.05). The median time to CCyR loss was 29.5 months in early CP, 10.3 months in group 6–12 months before IM, and 14.2 months in 12–60 months before IM group (p<0.01). Probability of CCyR loss was correlated with time to its achievement. CCyR was lost in 10% (rate 8.9% (7/78) of patients with CCyR obtained within 12 months of IM treatment with counterpart of 28% (18.9% (7/37)) for late-responders (CCyR after 12 months IM), p=0.02. The further subdivision by the time to CCyR achievement did not reveal any significant differences.
Among patients, who lost CCyR, only 2/14 (14%) patients progressed to blast crisis. One of them was treated with chemotherapy followed by allo-SCT. At present, he is still alive in CCyR and complete molecular response. Another patient with blast transformation was treated by high dose IM with chemotherapy. There is no response and patient died due to progressive disease.
From other patients: CCyR was re-obtained in 7 patients - in 5 patients on IM (2 pts on the same dose and 3 pts after IM dose escalation) and in 2 pts on second generation TKIs. One patient after IM dose escalation is not yet evaluable. Other 3 patients didn't respond either high dose IM or second generation TKIs, but are still alive in CML-CP. One patient lost from follow up.
Conclusions: Patients in CML-CP with CCyR has very good prognosis. Very few patients progressed and dead during several years. There are two factors, which influence the probability of CCyR loss: initiation of IM in early CP and CCyR in first year of treatment are favorable to good prognosis for CCyR durability.

Disclosures:
No relevant conflicts of interest to declare.