interest in topics related to the treatment of patients with cml (percent responding 9 or 10)
DESCRIPTION
Interest in Topics Related to the Treatment of Patients with CML (Percent Responding 9 or 10). Efficacy and tolerability of TKIs*. 42%. TKI-refractory CML. 39%. Sequencing of TKIs. 38%. New agents/regimens. 38%. Monitoring patients during therapy. 36%. Resistance mutations in BCR-ABL. - PowerPoint PPT PresentationTRANSCRIPT
Copyright © 2011 Research To Practice. All rights reserved.
Interest in Topics Related to the Treatment of Patients with CML (Percent Responding 9 or 10)
36%
36%
38%
38%
39%
42%
32% 34% 36% 38% 40% 42% 44%
Resistance mutations in BCR-ABL
Monitoring patients during therapy
New agents/regimens
Sequencing of TKIs
TKI-refractory CML
Efficacy and tolerability of TKIs*
*Tyrosine kinase inhibitors: Imatinib, dasatinib, nilotinib
Chronic Myeloid Leukemia (CML)
Susan M O’Brien, MD
IRIS 8-Year Update: Outcome After Imatinib
37%
Deininger M et al; Blood 2009;114(22):462.
Nilotinib vs Imatinib in Newly Dx CML (ENESTnd)
• Primary endpoint: MMR at 12 months
• Key secondary endpoint: Durable MMR at 24 months
• Other endpoints: CCyR by 12 months, time to MMR and CCyR, EFS, PFS, time to AP/BC on
study treatment, OS including follow-up
*Stratification by Sokal risk score
Imatinib 400 mg QD (n = 283)
Nilotinib 300 mg BID (n = 282)
RANDOMIZED*
Nilotinib 400 mg BID (n = 281)
• N = 846
• 217 centers
• 35 countries
Follow-up 5 years
Hughes et al. ASH 2010; abst #207
Nilotinib vs Imatinib in Newly Dx CML-CP (ENESTnd). Primary Endpoint - MMR Rate at 12 Months (ITT Population)
P < .0001
P < .0001
Pat
ien
ts w
ith
MM
R (
%)
Larson RA et al. J Clin Oncol 2010;28; Abstract 6501. Saglio G et al. N Engl J Med 2010;362; Abstract 2251.
IRIS 8-Year Results: Annual Rate of Events on Imatinib
• EFS = 81%• Freedom from progression to AP/BC = 92%-1 progression to AP/BC and 2 non-CML related deaths in year 8
Deininger et al. ASH 2009. Abs # 1126.
3.3
7.5
4.8
1.7
0.80.3
1.4 1.31.5
2.8
1.8
0.90.5
0 00.4
0
1
2
3
4
5
6
7
8
1 2 3 4 5 6 7 8
Year
EventLoss of C HR,Loss of MCyR,AP/BC ,Death during treat
AP/BCAP/BC
% W
ith C
CyR
Dasatinib versus Imatinib Study in Treatment-Naïve CML: DASISION (CA180-056) Study Design
● Primary endpoint: Confirmed CCyR by 12 months
● Secondary/other endpoints: Rates of CCyR and MMR; times to confirmed CCyR, CCyR and MMR; time in confirmed CCyR and CCyR; PFS; overall survival
Follow-up
5 yearsRandomized*
Imatinib 400 mg QD (n = 260)
Dasatinib 100 mg QD (n = 259)• N = 519
• 108 centers
• 26 countries
*Stratified by Hasford risk score
Shah et al. ASH 2010; abst #206.
DASISION: First-Line Dasatinib vs Imatinib in CML-CP CCyR Rate by 12 Months (ITT)
8377
7266
0
20
40
60
80
100
Dasatinib100 mg QD
Imatinib400 mg QDCCyR
(%)
Confirmed CCyRby 12 months
CCyRby 12 months
P = 0.0011P = 0.0067
Kantarjian. N Engl J Med 362: 2260, 2010.
DASISION: Progression to AP-BP (ITT)
• No patient who achieved MMR progressed to AP/BP CML
• 5 patients who achieved a CCyR progressed to AP/BP CML (2 dasatinib, 3 imatinib)
• Rates of progression-free survival at 18 mos: 94.9% for dasatinib and 93.7% for imatinib
2.3
3.5
0
2
4
6
Progressed to AP/BP, %
Dasatinib 100 mg QD
Imatinib 400 mg QD
n/N 6/259 9/260
Shah N et al. Blood 2010;116: Abstract 206.
100
DASISION: Confirmed CCyR (ITT)
Shah N et al. Blood 2010;116: Abstract 206.
P = 0.0086 P = 0.0366
77 7867 70
0
20
40
60
80
100
12 Months 18 Months
Confirmed CCyR, %
Dasatinib100 mg QD
Imatinib 400mg QD
Definitions of PFS-EFS in CMLDefinitions of PFS-EFS in CML
• Definitions of EFS/PFS vary in different studies• Definitions applied to 435 pts treated with frontline TKI
OccurrenceEFS-IRIS
TWP-ENEST
PFS-DASISION
EFS-MDACC
AP-BP on TKI + + + +
off TKI - - - +
Death on TKI +CML-related <30 d off TKI
Any cause +
off TKI -CML-related <30 d off TKI
<60 d off TKI +
Loss of CHR/MCyR + - + (also ↑WBC) +
• EFS-MDACC accounts for any event off TKI and any death on/off TKI
Kantarjian et al. Blood 2010:116; Abst #672.
Outcome According to Different Definitions of EFS/PFS
Kantarjian et al. Blood 2010:116;Abst #672.
Definitions Event 5-yr (%)
ENEST-TWP 15 96
IRIS-EFS 40 90
DASISION-PFS 43 89
MDACC-EFS 82 81
- Because EFS and PFS are important in determining whether new TKIs are better than imatinib in front-line therapy, precise and common definitions of these endpoints are needed.
- Because EFS and PFS are important in determining whether new TKIs are better than imatinib in front-line therapy, precise and common definitions of these endpoints are needed.
Data cut-off: 20Aug2010Hughes TP, et al. ASH 2010. Abstract 207.
Data cut-off: 20Aug2010Hughes TP, et al. ASH 2010. Abstract 207.
Data cut-off: 20Aug2010Hughes TP, et al. ASH 2010. Abstract 207.
Data cut-off: 20Aug2010Hughes TP, et al. ASH 2010. Abstract 207.
Data cut-off: 20Aug2010Hughes TP, et al. ASH 2010. Abstract 207.
DASISION: Grade 3/4 Cytopenia
11
2219
7
20
10
0
20
40
60
Anemia Neutropenia Thrombocytopenia
Patients, %
Dasatinib 100 mg QD
Imatinib 400 mg QD
100
• Grade 3/4 bleeding occurred in 2 patients on dasatinib and 3 patients on imatinib
• 6 patients on dasatinib and 3 patients on imatinib D/C Rx due to cytopenia
Shah N et al. Blood 2010;116: Abstract 206.
Common Nonhematologic Drug-Related AEs (≥10%)
AE, %Dasatinib 100 mg QD
N = 258Imatinib 400 mg QD
N = 258
All Grades Grade 3/4 All Grades Grade 3/4
Fluid retention 23 1 43 1
Superficial edema* 10 0 36 <1
Pleural effusion 12 <1 0 0
Myalgia† 22 0 38 1
Nausea 9 0 21 0
Vomiting 5 0 10 0
Diarrhea 18 <1 19 1
Fatigue 8 <1 11 0
Headache 12 0 10 0
Rash 11 0 17 1
* Includes 11 MedDRA preferred terms† Includes myalgia, muscle inflammation and musculoskeletal pain
Copyright © 2011 Research To Practice. All rights reserved.
What Clinicians Want to Know
A Live CME Event Addressing the Most Common Questions and Controversies in the Current Clinical
Management of Select Hematologic Cancers
Sunday, June 5, 20117:00 PM – 9:30 PMChicago, Illinois
Faculty
Sergio Giralt, MDJohn P Leonard, MD Lauren C Pinter-Brown, MD
ModeratorNeil Love, MD
Antonio Palumbo, MDSusan M O’Brien, MDProfessor Michael Hallek
Copyright © 2011 Research To Practice. All rights reserved.
What is your preferred initial systemic treatment for chronic-phase CML?
2%
4%
20%
10%
4%
11%
47%
0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50%
Other
Nilotinib 400 mg twice daily
Nilotinib 300 mg twice daily
Dasatinib 100 mg daily
Imatinib 800 mg daily
Imatinib 600 mg daily
Imatinib 400 mg daily
Copyright © 2011 Research To Practice. All rights reserved.
Have you discontinued imatinib, dasatinib or nilotinib for patients responding with sustained molecular CR?
3%
4%
10%
82%
0% 20% 40% 60% 80% 100%
Yes, other
Yes, after 5years
Yes, after 2years
No
Copyright © 2011 Research To Practice. All rights reserved.
What Clinicians Want to Know
A Live CME Event Addressing the Most Common Questions and Controversies in the Current Clinical
Management of Select Hematologic Cancers
Sunday, June 5, 20117:00 PM – 9:30 PMChicago, Illinois
Faculty
Sergio Giralt, MDJohn P Leonard, MD Lauren C Pinter-Brown, MD
ModeratorNeil Love, MD
Antonio Palumbo, MDSusan M O’Brien, MDProfessor Michael Hallek