Transcript AML Post Remission Therapy Risk Adapted

ANCO ASH 2005 Review
Acute Leukemias
Feb 22, 2006
Charles Linker MD
Abstract # 43
Mini-allo for AML
Herr et al
EBMT Review
Mini-allo for AML
EBMT Registry
n = 204
Age 58 (median)
Sib and MUD donors
Regimen - Flu/Bu, Flu/TBI
FU 13mo
1-yr TRM
1-yr Rel
1-yr LFS
1-yr OS
15%
34%
50%
62%
Abstract # 47
Mini-allo for AML
Shimoni et al
Tel Hashomer, Israel
Mini-allo AML
Israel
n = 67
Age > 55
Sib and MUD donors
Regimen - Flu/Bu
FU 22mo
2-yr TRM
2-yr OS
8%
47%
If CR1: 2-yr OS 80%, TRM 0%
CALGB 100103
Phase II Study of mini-allo
for AML CR1, age > 60
Study Chair: Steve Devine
CTN co-chair: Sergio Giralt
CALGB 100103
Background - 1
• Poor results of chemotherapy
• No signs of progress in chemotherapy
• New approaches are warranted
CALGB 100103
CALGB background data
• Analysis of 600 CALGB AML age > 60 with
cytogenetics
CR 50%
5-year OS 7% !!!
Cytogenetics predictive of outcome
0.2
0.4
0.6
0.8
P< 0.001
P<0.001
<5
a bn
or malitie s ( n=273 )
<5
Abnormalities
55 Abnormalities
>=
a bn or malitie s ( n=23)
0.0
Probability of Remaining Disease-Free
1.0
AML CR1, age > 60
DFS by Cytogenetics
0
5
10
Time ( Ye ar s )
15
1.0
AML CR1, age > 60
OS by Cytogenetics
0.6
0.4
0.2
C BF abn. ( n=21)
< 5 abn, no C BF, no - 7 (n=464)
0.0
Probability of Surviving
0.8
p<0.0001
- 7 ( n=21)
>= 5 abn. ( n=85)
0
5
10
Time ( Year s )
15
1.0
AML CR1, age > 60
OS by Age
0.6
0.4
0.2
60-69 y ears (n=354)
0.0
Probability of Surviving
0.8
P= 0.0001
70-79 y ears (n=218)
>=80 y ears (n=28)
0
5
10
Time (Years )
15
CALGB 100103
Background - 2
• Results in best group are still poor (n = 276)
CR1
Age 60-75
Receive first consolidation on randomized trial
• 2-year DFS 24%
• 3-year DFS 17%
CALGB 100103
Eligibility - 1
• AML CR1
Prior MDS, t-AML allowed
< 2 cycles induction
< 2 courses consolidation
< 6 months in CR1
exclude APL, prior MPD
• Age 60-74
• Matched sibling or 10/10 MUD donor
CALGB 100103
Eligibility - 2
• PS 0 - 2
• Adequate organ function
DLCO > 40%
EF > 30%
Creatinine clearance > 40
Bili < 2.0
AST < 3x normal
CALGB 100103
Preparative Regimen
•
•
•
•
Fludarabine 30 mg/m2 x 5
Busulfan 0.8 mg/kg IV x 8
Thymoglobulin 2.5 mg/kg x 3
Stem cell infusion
days -7 to -3
days -4 to -3
days -4 to -2
day 0
CALGB 100103
GVH Prophylaxis
• Tacrolimus
• MTX 5 mg/m2
• Taper tac
day - 2 to +90
days, +1, 3, 6, 11
day +90 to +150/+180
CALGB 100103
Statistics
• Primary objective 2-year DFS > 35%
90% power to exclude DFS < 20%
• Accrual goal = 61
• Stopping rules for TRM
Assume true TRM 20%
Unacceptable TRM 40%
CALGB 100103
• Currently active in CALGB
sib donors only
• Amendment in process
Add CTN
Add MUD
Mini-allo for AML, age > 60
•
•
•
•
•
Currently treatments work poorly
Mini-allo is feasible
Several pilot studies show DFS > 40%
Deserves testing in Group setting
CALGB 100103 is last chance for USA study
Abstract # 146
Ph+ ALL
Dellanoy et al
GRALL, France
Ph+ ALL,age > 55
Treatment
• Pre-phase
Prednisone x 1 week
• Induction
CyDVP
Imatinib 600 x 2 mo
• Consolidation
10 blocks of chemo
2 x 2 mo imatinib
• CNS-P
i.t. mtx + cranial RT
Ph+ ALL, age > 55
Results
N = 30
Age 66 (58 - 78)
FU 15mo
CR 20/29
( vs 6/21 historical control)
1-yr OS 71%
(11% control)
1-yr EFS 57%
(5% control)
ASCT for high-risk ALL
Protocol 9501 & SOC
1.0
0.8
0.6
EFS 44%
0.4
0.2
0.0
0
2
4
6
YEARS
8
10
10/25/05
Protocol 9501 SOC for Ph+
Effect of Imatinib
1.0
0.8
Imatinib EFS 71%
0.6
0.4
pre-Imatinib EFS 20%
0.2
0.0
0
2
4
6
YEARS
8
10
10/25/05
Ph+ ALL
Role of Imatinib
• Plays major role in induction
Safe to combine with chemotherapy
Increases remission rate
• Encouraging results post-remission
• May play role in transplant
Allo transplant is treatment of first choice
Patients get to transplant in remission
May reduce relapse rate
ASCT being tested in CALGB 10001
May allow PCR neg stem cells for ASCT
Abstract # 150
Nelarabine for T-ALL
Goekbuget et al
GMALL, Germany
CALGB 19801
De Angelo et al
ASH #743 (2002)
• Eligibility
T-ALL or T-LL
Relapse or refractory
• Treatment
Nelarabine (GW 506U) 1.5g/m2 days 1, 3, 5
q3 weeks x 2 cycles
Responders may get additional 2 cycles
• Results
10/38 CR (26%)
MDCR 10mo
1-yr DFS 40%
Nelarabine
Patients and Treatment
• n = 53
• Age 31 (19 - 81)
• Disease category:
First relapse 36
Second relapse 7
Relapse after transplant 7
Refractory 3
• Treatment:
Nelarabine 1.5g/m2 days 1, 3, 5
Nelarabine
Results
25/53 CR (47%)
19/25 Cr go to transplant
OS 16%
OS of CR 27%
Nelarabine for T-ALL
• Important new agent
• Good choice for relapse
• Should be tested up front