Poster Presentation

1. Quality of Life (QoL), Efficacy and Safety of Treatment with
Dasatinib as Front-line Therapy or after Early Switching from
Imatinib in Patients with Chronic Myeloid Leukemia in Chronic
Phase (CP CML): a Real World Data
Ionova T.1,2, Bulieva N.3, Vinogradova O.4,5,6, Zinkovskaya A.2, Lipatova D.2, Lomaia
E.7, Nikitina T.1,2, Novitskaya N.4, Trifonova E.8, Usacheva E.9, Chukavina M.10,
Shumkova M.11
1Saint-Petersburg MultiSpeciality Medical Center, Saint-Petersburg State University, Saint-Petersburg
2Multinational Center for Quality of Life Research, Saint-Petersburg
3 Institute of Medicineof Immanuel Kant Baltic Federal University, Kaliningrad
4Hematological Moscow City Center, Botkin City Clinical Hospital, Moscow
5Centre of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow
6Pirogov Russian National Research Medical University, Moscow
7Federal Almazov North-West Medical Research Center, Saint-Petersburg
8Vladimirskii Moscow Regional Research and Clinical Institute, Moscow
9R.M. Gorbacheva Memorial Institute of Children Hematology and Transplantation of Pavlov Saint
Petersburg State Medical University, Saint-Petersburg
10Regional hospital, Kolomna, 11Regional clinical hospital, Kurgan
6-9 April, 2017
Saint-Petersburg

2. Background
• Dasatinib as a first-line is a promising treatment option for CP CML pts.
Assessment of benefits and risks of this treatment regimen both from physician’s
and patient’s perspective sounds worthy.
• The efficacy and safety of front- line treatment with dasatinib in CP CML pts as
well as pts’ quality of life (QoL) has been studied in clinical trials. It’s of
worthwhile to obtain the above information in a real-world setting.

3. Objectives
• To study QoL and clinical outcomes of dasatinib as
a front-line treatment in CP CML pts in a real world
setting
•«Quality of life, symptom profile and adherence to treatment in
patients with newly-diagnosed chronic myeloid leukemia in
chronic phase during dasatinib treatment»
Multicenter prospective observational study in a real-world setting
Primary outcomes – QoL, symptom profile
Secondary outcomes – hematological response, molecular response, cytogenetic
response, AEs frequency and severity
Participants – 13 centers in 10 cities in Russian Federation
Study terms: 2014-2017
*Supported by grant of BMS

4.  Generic QoL questionnaire – RAND SF-36
•Physical Functioning (PF)
•Role Physical Functioning (RPF)
•Bodily Pain (BP)
•General Health (GH)
Patient-reported outcomes
Study time-points
Baseline – before treatment with dasatinib
Follow-up – 1, 3, 6 and 12 mos after dasatinib treatment start
•Vitality (VT)
•Social Functioning (SF)
•Role Emotional Functioning (REF)
•Mental Health (MH)
Integral QoL Index
Patients and Methods
Study tools and time-points
Response to treatment
Hematological, cytogenetic and molecular response (HR, CyR, MR) rates in
accordance with international clinical recommendations (European
LeukemiaNet recommendations for the management of CML; 2013).
Adverse events (AEs)
Prevalence and severity in accordance with NCI CTCAE v. 3.0.

5. Total number, N 37
Median age (interquartile range), years old 47 (19–74)
Male, n (%) 22 (60)
Median disease duration (interquartile range), mos 4 (3-8)
Patient groups depending of TKI treatment, n (%):
-TKI-naive pts
-Early switch to dasatinib (less than in 9 mos)
18 (49)
19 (51)
Sokal risk at diagnosis, n (%)
- low
- intermediate
- high
13 (35)
15 (40)
9 (25)
Median duration of dasatinib treatment – 12 mos (0.25 – 12)
Median duration of follow-up from diagnosis – 17 mos (0.25 – 36)
Results
Patients’ characteristics
Treatment prescribed
Dasatinib 100 mg daily, as a first-line or after early switch after failure of imatinib treatment

6. Results
At median follow-up of 12 mos
• The rate of stable complete HR – 93.5% (95% CI: 84.8–100%);
• The rate of stable complete CyR – 80% (95% CI: 62.5–97.5%);
• The rate of major MR – 55.6% (95% CI: 36.9–74.3%).
Clinical Efficacy of Dasatinib as Front-line Therapy or after Early Switching from Imatinib
in Patients with Chronic Myeloid Leukemia in Chronic Phase (CP CML)
 Number of pts completed the study in accordance with the protocol – 26 (70%)
 Number of pts discontinued prematurely : because of SAEs – 2 (5%), due to resistance
to dasatinib – 3 (8%)
 No cases of death during the follow-up

7. AEs
All grades AEs,
CTCAE v3.0, n (%)
Grades 3-4 AEs
CTCAE v3.0, n (%)
Fatigue 5(15.6) –
Short breath 3(9.4) –
Rash 3(9.4) –
Arthralgia/Myalgia 2(6.3) 1(3.1)
Nausea/Vomiting 2(6.3) 1(3.1)
Gastrointestinal 2(6.3) 1(3.1)
Dizziness 2(6.3) 1(3.1)
Memory impairment 2(6.3) –
Pruritus/itching 2(6.3) –
Hemorrhage, GI 2(6.3) –
Alopecia 2(6.3) –
Weight gain 2(6.3) –
• Hematological and non-hematological AEs were registered in 13 pts (40.6%) and were the
same as in clinical trials, in the most cases AEs were non-severe/moderate;
• No pleural effusion has been revealed during treatment;
• Serious AEs: grade 2 lung edema (n=1), grade 2 duodenum hemorrhage (n=1)
• No grade 4 AEs.
Safety of Dasatinib Treatment as Front-line Therapy or after Early Switching from
Imatinib in Patients with Chronic Myeloid Leukemia in Chronic Phase (CP CML)
Results

8. *
*
* 0
20
40
60
80
100
PF
RPF
BP
GH
VT
SF
REF
MH CP CML patients
Healthy controls
*p<0.05
• QoL in CP CML pts at baseline was lower as compared to healthy controls: Integral QoL
Index – 0.426 vs 0.547 (p=0.02). CP CML pts had significantly worsened physical
functioning, role physical functioning and role emotional functioning than healthy
controls: 78.1 vs 90.8, 51.6 vs 81.3, 57.4 vs 85.2 (p<0.05).
• No QoL differences were found between TKI-naive and early switched pts before
dasatinib treatment (p>0.05).
QoL in CP CML Patients Before Dasatinib Treatment as Compared to Healthy Controls
Results

9. Results
• During treatment QoL parameters were stable or improved.
• Integral QoL Index during 12 mos of treatment significantly improved (GEE, with
adjustment for age, gender, the Sokal score and comorbidities; p=0.007) –
0.431 at base-line vs 0.531 at 12 mos.
• At 12 mos Integral QoL Index became comparable to Integral QoL Index of healthy
controls (p>0.05).
QoL changes during dasatinib treatment in TKI-naive CP CML patients
and in patients early switched after imatinib treatment

10. Conclusion
• Benefits and risks of front-line treatment with
dasatinib in CP CML both from physician’s and
patient’s perspective were demonstrated.
• Data on efficacy and safety of dasatinib as a front-line
treatment in a real world setting are similar to the
ones in clinical trials.
• Dasatinib treatment with the median duration of 12
months is accompanied with QoL
stabilization/improvement.