Adolescent and Young Adult Leukemia
Pediatric vs. Adult Protocols
Economic and psychosocial factors
may contribute to the poor outcomes
observed in the AYA leukemia popula-
tion compared with the pediatric
population, but the most critical – and
most easily modifiable – factor is
the type of protocol used in each age
group. Within the past decade, research
has consistently shown that, despite the
biologic and social differences between
pediatric and AYA patients, both
groups derive a greater benefit from
pediatric-directed protocols.
Many of the most commonly used
pediatric regimens are modeled off the
Berlin-Frankfurt-Munster regimen,
with a heavy reliance on nonmyelosup-
pressive agents, including vincristine,
steroids, and asparaginase, delivered in
low single doses, but in high cumulative
doses of each individual agent.
Adult protocols, however, are
characterized by greater use of
myelosuppressive agents, including
156
ASH Clinical News
cyclophosphamide and anthracyclines, with
little or no use of asparaginase, which is
perceived to be prohibitively toxic in adults,
Dr. Advani explained.
She also noted that pediatric regimens
typically include more steroids, longer
intrathecal chemotherapy, and, typically,
longer maintenance phases than adult treat-
ment protocols. “Paradoxically, pediatric-
directed regimens are more aggressive than
adult protocols,” Dr. Stock said. “It’s all the
same medications that most adult groups
have studied, but in different proportions
and on different schedules.”
Location, Location, Location
With so much evidence favoring pediat-
ric protocols for patients younger than
age 40, “most people – myself included
– would say that that problem is pretty
much solved,” Dr. Gupta said. “If you
are an AYA patient with ALL, then you
should be receiving a pediatric protocol.”
The next problem to tackle is where
patients should be undergoing this type
of treatment. Most AYA patients undergo
treatment at adult centers, where provid-
ers may not be well-versed in pediatric-
based protocols. Dr. Gupta pointed out
that his research group, along with several
For adult patients with relapsed or refractory
CLL or SLL after at least 2 prior therapies
Experience the effi cacy
TM
of COPIKTRA (duvelisib)
The fi rst and only oral dual PI3K-δ and PI3K-γ inhibitor 1
Patients achieved a >7 month median PFS advantage with oral COPIKTRA vs IV ofatumumab
in the pivotal phase 3 DUO trial 1,2 *
COPIKTRA 25 mg BID
(n=95; SE: 2.1)
Ofatumumab
(n=101; SE: 0.5)
100
16.4-MONTH
90
perhaps they don’t want to fall behind their
peers in their classes because they have to
take time away to undergo treatment.”
Dr. Advani said that the same is true
for patients in their 30s. “Even though they
are young, these patients may be married
and trying to support their own families, so
this can be a very difficult time to be going
through a diagnosis and treatment of ALL.”
Navigating these psychosocial challenges
requires time and expertise that not all
health-care providers who typically treat
younger or older patients can provide.
Pediatric patients are more likely
than older patients to be adherent
with their treatment regimens; liv-
ing with their parents means having
someone available to ensure patients
are taking their medications or getting
to appointments. 7 “However, AYA pa-
tients are often independent and have
fewer support systems in place,” Dr.
Stock said. “These are long, arduous
therapies that can take years to com-
plete and [require] frequent visits to
the physician’s office, so getting people
through treatment is a challenge.”
AYA patients also are more likely
than any other age group to lack health
insurance. For example, in 2008, 28.6
percent of people aged 18 to 24 years
and 26.5 percent of those between 25
and 34 years lacked coverage; by com-
parison, less than one-fifth of people
aged 35 to 64 years, and less than one-
tenth of children under age 18 were
uninsured. 8 Experts say this may be
changing though, since the Affordable
Care Act allowed children to stay on
their parents’ insurance until age 26.
Although the implications haven’t
been fully studied yet, Dr. Stock said she
hopes this change makes it easier for
older young adults to obtain insurance
coverage for their medications.
80
MEDIAN PFS WITH COPIKTRA
70
Censored
60
• Safety was based on the
comprehensive overall study
population (N=319) 1
50
40
30
9.1-MONTH
20
10
MEDIAN PFS WITH OFATUMUMAB
0
0
NUMBER OF
PATIENTS AT RISK:
3
6
9
12
• Effi cacy was based on a subanalysis
of patients with at least 2 prior lines of
therapy, where the risk:benefi t ratio
appeared greater in this more heavily
pretreated population (n=196) 1
60% risk reduction
with COPIKTRA
(HR: 0.40; SE: 0.2)
15
18
21
24
27
30
33
36
MONTHS
Visit COPIKTRAHCP.com/dual to learn more
*Kaplan-Meier estimate.
CLL, chronic lymphocytic leukemia; δ, delta; γ, gamma; HR, hazard ratio; IV, intravenous; PI3K, phosphoinositide 3-kinase;
PFS, progression-free survival; SE, standard error; SLL, small lymphocytic lymphoma.
IMPORTANT SAFETY INFORMATION
WARNING: FATAL AND SERIOUS TOXICITIES: INFECTIONS, DIARRHEA OR COLITIS, CUTANEOUS REACTIONS, and
PNEUMONITIS
• Fatal and/or serious infections occurred in 31% of COPIKTRA-treated patients. Monitor for signs and symptoms of
infection. Withhold COPIKTRA if infection is suspected.
• Fatal and/or serious diarrhea or colitis occurred in 18% of COPIKTRA-treated patients. Monitor for the development of
severe diarrhea or colitis. Withhold COPIKTRA.
• Fatal and/or serious cutaneous reactions occurred in 5% of COPIKTRA-treated patients. Withhold COPIKTRA.
• Fatal and/or serious pneumonitis occurred in 5% of COPIKTRA-treated patients. Monitor for pulmonary symptoms and
interstitial infi ltrates. Withhold COPIKTRA.
WARNINGS AND PRECAUTIONS
Infections: Serious, including fatal (18/442; 4%), infections occurred in 31% of patients receiving COPIKTRA 25 mg BID (N=442).
The most common serious infections were pneumonia, sepsis, and lower respiratory infections. Median time to onset of any grade
infection was 3 months (range: 1 day to 32 months), with 75% of cases occurring within 6 months. Treat infections prior to initiation of
COPIKTRA. Advise patients to report new or worsening signs and symptoms of infection. For grade 3 or higher infection, withhold
COPIKTRA until infection is resolved. Resume COPIKTRA at the same or reduced dose. Serious, including fatal, Pneumocystis
jirovecii pneumonia (PJP) occurred in 1% of patients taking COPIKTRA. Provide prophylaxis for PJP during treatment with COPIKTRA
and following completion of treatment with COPIKTRA until the absolute CD4+ T cell count is greater than 200 cells/µL. Withhold
COPIKTRA in patients with suspected PJP of any grade, and permanently discontinue if PJP is confi rmed. Cytomegalovirus (CMV)
reactivation/infection occurred in 1% of patients taking COPIKTRA. Consider prophylactic antivirals during COPIKTRA treatment to
prevent CMV infection including CMV reactivation. For clinical CMV infection or viremia, withhold COPIKTRA until infection or viremia
resolves. If COPIKTRA is resumed, administer the same or reduced dose and monitor patients for CMV reactivation by PCR or antigen
test at least monthly.
Diarrhea or Colitis: Serious, including fatal (1/442; <1%), diarrhea or colitis occurred in 18% of patients receiving COPIKTRA 25 mg
BID (N=442). Median time to onset of any grade diarrhea or colitis was 4 months (range: 1 day to 33 months), with 75% of cases
occurring by 8 months. The median event duration was 0.5 months (range: 1 day to 29 months; 75 th percentile: 1 month). Advise
patients to report any new or worsening diarrhea. For patients presenting with mild or moderate diarrhea (Grade 1-2) (i.e., up to
B:15
T:15
S:14