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Treating Young Adults Treating Young Adults with Acute with Acute
Lymphoblastic Lymphoblastic Leukemia:Leukemia:
Is this progress?Is this progress?
M. Rytting, M.D.M. Rytting, M.D.M.D. Anderson Cancer CenterM.D. Anderson Cancer Center
Why have a trial of therapy for ALL Why have a trial of therapy for ALL in this population? in this population?
What therapy should be the standard What therapy should be the standard arm? arm?
After the first trial, what is next?After the first trial, what is next?
LymphomaLymphoma
LeukemiaLeukemia
Germ CellGerm Cell
SarcomaSarcoma
Brain Brain
7%7%
TestisTestis
9%9% OvaryOvary
7%7%
Hodgkin'sHodgkin's
16%16%
NHLNHL
8%8%ALLALL
6%6%AMLAML
5%5%CNSCNS
10%10%Soft Tissue SaSoft Tissue Sa
7%7%
OsteosarcomaOsteosarcoma
5%5%
Ewing'sEwing's
2%2%
MelanomaMelanoma
7%7%
ThyroidThyroid
OtherOther
12%12%
Cancers in Young Adults, Age 15-19 Cancers in Young Adults, Age 15-19 Years Years SEER, 1975-1998, U.S.SEER, 1975-1998, U.S.
National Cancer Mortality Reduction1990-1998
Age (Years)
2.8%2.6%
1.8%
0.9%
1.5%
0.4%
1.1%
1.5%
0%
1%
3%
2%
Average Annual
% Reduction
0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39
ALL in AYA PatientsALL in AYA Patients
What age range should be targeted?What age range should be targeted? Pediatric evidence supports at least up to age Pediatric evidence supports at least up to age
2121 Above 21 and under __?__ is the Above 21 and under __?__ is the
experimental groupexperimental group This group is generally going to be This group is generally going to be
underinsuredunderinsured They do not go to pediatric clinics or They do not go to pediatric clinics or
hospitals (though some of them could hospitals (though some of them could fool you)fool you)
Adult Trials in ALLAdult Trials in ALL
ALL represents about 1% of adult ALL represents about 1% of adult malignancymalignancy
Stratification by age not usually Stratification by age not usually done or reporteddone or reported
The cure rate for all adults as a The cure rate for all adults as a group is consistently around 40%group is consistently around 40%
Larson R, et al. Blood 1998, 92: 1556.Larson R, et al. Blood 1998, 92: 1556.
Rowe JM, et al. Blood 2005, 106: 3760.Rowe JM, et al. Blood 2005, 106: 3760.
Copyright ©2005 American Society of Hematology. Copyright restrictions may apply.
Overall survival by age
Rowe, J. M. et al. Blood 2005;106:3760-3767
MDACC curveMDACC curve
.
Thomas X et al. JCO 2004;22:4075-4086
©2004 by American Society of Clinical Oncology
Adult Trials with Adult Trials with ModificationsModifications
Outcomes by therapy for younger patients (age younger than 60 years) with Philadelphia chromosome–negative precursor B-lineage acute lymphoblastic leukemia.
Thomas D A et al. JCO 2010;28:3880-3889
©2010 by American Society of Clinical Oncology
Retrospective Analysis of Retrospective Analysis of the Adolescent/Young Adult the Adolescent/Young Adult
ExperienceExperience
ALLU.S. CCG vs CALGB
• CALGB – CR 93%– EFS (6 yr) 38%– Outcome Same
• Age 21-29 yrs at Dx
• Stock W, Blood 96, 476a.
• CCG– CR 96%
– EFS (6 yr) 64%
A L LF r a n c e F R A L L E v s L A L A
Copyright ©2008 Ferrata Storti Foundation
Usvasalo, A. et al. Haematologica 2008;93:1161-1168
(A) Event-free survival (EFS) and (B) overall survival (OS) of the study patients treated with pediatric and adult protocols
Recent Pediatric Trial Recent Pediatric Trial Results for Adolescents Results for Adolescents
with ALLwith ALL
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 1 2 3 4 5 6 7 8 9
CCG-1961 Augmented vs. Standard BFM EFS outcome(Age 16+ subset)
AUG BFM (N=87)
STD BFM (N=76)
Pro
ba
bil
ity
Years Followed (from Rand.)
5-Yr EFS
AUG BFM 81.3% (s.d.7.0%)
STD BFM 63.2% (s.d.9.3%)Log Rank p=.08
Applying Pediatric-based Applying Pediatric-based Therapy to Young Adults Therapy to Young Adults
with ALL with ALL There are currently a handful of There are currently a handful of
published studies, and the number is published studies, and the number is growinggrowing Some ongoing studies are currently in Some ongoing studies are currently in
abstract formabstract form How many randomized?How many randomized? Patient characteristics? Patient characteristics? Subsets that do better? Subsets that do better?
.
Ribera J et al. JCO 2008;26:1843-1849
©2008 by American Society of Clinical Oncology
Event-free survival (EFS) and overall survival (OS).
Huguet F et al. JCO 2009;27:911-918
©2009 by American Society of Clinical Oncology
Chang J, et al. Leukemia and Lymphoma, 2008; 49(12):2298Chang J, et al. Leukemia and Lymphoma, 2008; 49(12):2298
So, start a trial.So, start a trial.
What regimen to use? What regimen to use? ObstaclesObstacles Compliance (patient and physician)Compliance (patient and physician) InsuranceInsurance Funding?Funding?
Overall Survival
00.0
0.2
0.4
0.6
0.8
1.0
<=25 (n=44)>25 (n=16)
1 year 2 years 3 years
Time from Start of Therapy
Fra
ctio
n s
urv
ival
CRD by age (n=58)
00.0
0.2
0.4
0.6
0.8
1.0
<=25 (n=42)>25 (N=16)
1 year 2 years 3 years
Time
Fra
ctio
n s
urv
ival