CLINICAL NEWS
Twenty-three percent of lean patients had MRD (defined as ≥0.1%
leukemia cells) after induction therapy, compared with 27 percent of
overweight and 44 percent of obese patients.
On univariate analysis, obese children with BP-ALL were more than
two-and-a-half times more likely to have residual leukemia as measured
by MRD (odds ratio = 2.62 [95% CI 1.24-5.50; p=0.042]). This association held true when the authors conducted two separate multivariate
analyses that took into account patients’ age, sex, ethnicity, white blood
cell count, BMI, and cytogenetics.
Event-free survival up to five years was also significantly longer for
children who were lean at the time of diagnosis. Additionally, the presence of MRD after induction therapy increased a patient’s risk of an event
(hazard ratio = 3.48; 95% CI 1.00-12.12; p=0.45). “Overweight or obesity
may thus continue to exert an adverse impact on event-free survival even
following the induction phase,” the authors wrote.
The effects of adiposity on survival in pediatric ALL, therefore,
start early – already present and significant at the time of diagnosis –
and endure through the next treatment phase. According to Dr. Orgel
and colleagues, this raises the question of “whether obese patients
should be considered as a higher risk group from time of diagnosis,
analogous to adolescents, who could potentially benefit from more
intensive therapy during induction.”
What explains this relationship between obesity and poorer outcomes
with BP-ALL? While the mechanism has yet to be fully elucidated, the
authors suggest that adipocyte-leukemia interactions may mediate the
adverse impact of obesity noted in pediatric ALL.
References
• Orgel E, Tucci J, Alhushki W, et al. Obesity is associated with residual leukemia following induction therapy for childhood
B-precursor acute lymphoblastic leukemia. Blood. 2014 October 27. [Epub ahead of print]
Remission Duration Key to Survival in CLL After FCR
In spite of the efficacy of
the treatment regimen of
fludarabine, cyclophosphamide,
and rituximab (FCR) in chronic
lymphocytic leukemia (CLL),
most CLL patients are likely to
relapse. Guidance is needed for
managing these patients at the
time of FCR failure.
To define optimal salvage
therapy – and to identify
patients who would not benefit
from retreatment with FCR –
Constantine S. Tam, MD, MBBS,
of Peter MacCallum Cancer
Centre in Melbourne, Australia,
and colleagues conducted a
retrospective study of 300 CLL
patients enrolled in a phase II
study of FCR. They found that the
duration of first remission (CR1)
was a key determinant of survival
following disease progression and
first salvage.
Patients with a short CR1 (<3
years) had a truncated survival,
irrespective of salvage therapy
received, while patients with a
long CR1 (≥3 years) – and who
had salvage treatment with either
repeat FCR or lenalidomide-based
therapy – had a median survival
exceeding five years.
The researchers also found that
patients with CR1 <3 years had a
ASHClinicalNews.org
median post-salvage survival of 13
months, compared with 63 months
for patients with CR1 ≥3 years
(p<0.001). After analyzing salvage
therapy data spanning 13 years,
they confirmed the prognostic
significance of CR1 was not due
to an effect of the era in which a
patient was treated.
What is the take-home message
from this study? According to
Dr. Tam, “Patients with <3-year
remission after FCR are refractory
to standard treatments and should
be prioritized for novel therapies
and/or transplantation.” In
addition, “Retreatment with FCR
after three years is acceptable,” he
told ASH Clinical News.
In further analyses of salvage
therapy, the group found that
patients receiving either FCRbased or lenalidomide-based
salvage had superior survival
to those who received other
regimens, with a median survival
of 82 months versus 29 months
(p<0.001), respectively.
Finally, the authors noted
that those patients with specific
cytogenetic changes, such as
17p deletion or 11q deletion
experienced inferior postprogression survival, compared
with other cytogenetic subgroups.
Patients with shorter-term
remission after FCR should be
prioritized for novel therapies
and/or transplantation.
Given the results of this study,
expanding the ultra-high risk
category of CLL patients to include
those with early FCR failure,
as well as patients with TP53
aberrations, may be a practical
and effective way to identify
those who may benefit most from
novel, high-cost therapies (such as
ibrutinib and idelalisib).
“These promising new therapies
should be targeted specifically
to groups where they can make
the greatest contribution, such
as those not suitable for FCR
retreatment,” Dr. Tam and
colleagues wrote. In terms of how
the results of the current study can
aid in the development of those
therapies, Dr. Tam pointed out that
“It would concentrate novel agent
developm