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