poster presentation

1. Efficacy of third line target therapy
in patients with chronic myeloid
leukemia in chronic phase after
failure or intolerance to two
previous TKI in clinical practice
Lazorko N., Lomaia E., Zaritskey A., Ovsyannikova E. , Matiukhina N., Sbitiakova E.,
Shuvaev V., Martynkevich I., Fominykh M., Machyulaitene E., Abdulkadyrov K.
Federal Almazov North-West Medical Research Centre
Russian Research Institute of Hematology and Transfusiology
I.P. Pavlov First St. Petersburg State Medical University
Saint-Petersburg
Russian Federation

2. Introduction
Overall survival of patients in
chronic phase chronic
myeloid leukemia
dramatically increased in the
era of tyrosine kinase
inhibitors. Nearly half of
patients discontinue first line
Imatinib and half of them
subsequently failure
treatment with second line
TKI. It seems that 20-25% of
patients with chronic phase
chronic myeloid leukemia
need third line therapy.
ELN recommendations 2013

3. Inclusion criteria
• Chronic myeloid leukemia, chronic phase, Ph+.
• Age ≥18 years.
• Resistance or intolerance to any 2 tyrosine kinase
inhibitors (imatinibdasatinibnilotinib).
• No prior steam cell transplantation.
Why these patients were not transplanted after 2nd line?
1. Patients’ decision – 16 pts.
2. Age >65 and comorbidities – 12 pts.
3. Needed time for donor searching – 9 pts.
4. Switching in partial CyR – 8 pts.
5. Absence of matched donor (related or unrelated) – 6 pts.
6. Unknown (patients from other regions) 2 pts.

4. Patients’ characteristics
Patients N=53
Female/male 33/20 patients
Median age at diagnosis 46,8 (23-88) years
Imatinib resistant/intolerant 43/10 patients
2nd line resistant/intolerant 38/15 patients
Status at 3rd
line start
Median CML duration 55 (2-314) months
Mutations (performed in 26 pts) 9 mutations in 6 pts, NO T315I
CHR 64,2% (34/53)
Minor+minimal CyR 15,1% (8/53)
Partial CyR 15,1% (8/53)
CCyR without MMR 13,2% (7/53)
Third line treatment
Median duration of 3rd line TKIs 21 (1-67) months
Nilotinib as 3rd line 33,9% (18/53)
Dasatinib as 3rd line 56,6% (30/53)
Bosutinib as 3rd line 9,4% (5/53)

5. Response rate on third line treatment
Major molecular
response (MMR)
was achieved and
remained stable
in 6/17 (35%) pts
with CCyR.
CCyR and time before 3rd line
up to two years
more than two years
p=0,038
68%
34%
Among patients with the duration
of CML before third line less than
2 years probability of CCyR was
higher, than in others: 68% and
34% respectively, p<0,05.

6. Reasons for 3rd line discontinuation
Therapy was stopped
in 21 patients

7. Progression and survival:
• Progression to accelerated or blastic phases during
therapy or after discontinuation occurred in 22,6%
(12/53) patients.
• Median time to progression was 14,7 months (0.1-46).
• Overall 16/53 (30,2%) patients dead.
• Overall survival probability by 2 years from third line TKIs
was 67%.
• No patients with MCyR progressed or dead.

8. Overall survival from diagnosis and
death reasons
16 deaths
Progression;
12; 75%
Transplant-
related; 2;
12%
Non-CML; 2;
13%
Median duration of all TKI treatment is 85 (15-166) months.

9. Ongoing
treatment
(n=32)
Treatment discontinued
(n=21)
Stable
CCyR
(n=8)
Allo-SCT
(n=7)
4rth
line TKI
(n=2)
Stable
MCyR
(n=9)
Stable CHR
(CyR<MCyR)
(n=15)
Alive in
MMR
(n=5)
Non-TKI
treatment
(INF, HU) in
T315I pts
(n=2)
Death
(n=16)
3rd line TKI (n=53)
Patients’ status at the last follow-up

10. Conclusions
• Early switch to the next line of TKI treatment lead
to better response to the therapy.
• Using of 3rd line TKIs lead to CCyR achievement in
10% of cases in patients without partial
cytogenetic response at the start of the therapy
• Third-line TKI therapy might be effective in some
heavily pretreated pts. This strategy should be
used in the absence of any other therapeutic
options.