CLINICAL NEWS
TP53 Mutations Identify Patients With “Highly Aggressive” Mantle Cell Lymphoma
Patients with TP53-mutated mantle cell
lymphoma (MCL) have poor overall
survival (OS), compared with patients
without the mutation. In an analysis of
two trials evaluating standard treat-
ment regimens consisting of modern
cytarabine-containing induction therapy
followed by autologous hematopoietic
cell transplantation (AHCT), the pres-
ence of these mutations identifies
patients who do not benefit from
aggressive chemoimmunotherapy,
noted Christian W. Eskelund, MD,
from the Department of Hematol-
ogy at Rigshospitalet in Copenhagen,
Denmark, and co-authors. 1
“The intensified standard-of-care
regimens for younger [patients with]
MCL do not overcome the deleteri-
ous effects of TP53 mutations,” the
researchers wrote in their report
published in Blood. Given the poor
results seen in this patient popula-
tion, they “should be considered for
alternative frontline treatment.”
The authors analyzed bone marrow
samples from the 183 patients (median
age = 56 years; range = 29-65 years)
enrolled in the Nordic MCL2 and
Nordic MCL3 trials who were evalu-
able for genetic analyses. The MCL2
and MCL3 trials included a total of
319 patients with MCL who were
treated with an induction phase of
alternating R-maxi-CHOP (rituximab
[R], cyclophosphamide, daunorubicin,
vincristine, prednisone) and R-high-
dose cytarabine, followed by high-dose
chemotherapy with BEAM (carmus-
tine, etoposide, cytarabine, melphalan)
or BEAC (high-dose carmustine,
etoposide, cytarabine, cyclophospha-
mide) and AHCT.
In the MCL2 and MCL3 cohorts,
over a median follow-up of 9.2 years,
“The intensified
standard-of-
care regimens
for younger
[patients with]
MCL do not
overcome the
deleterious
effects of TP53
mutations.”
—CHRISTIAN W. ESKELUND, MD
ASHClinicalNews.org
the median overall survival (OS) and
progression-free survival (PFS) were 12.5
years and 8.2 years, respectively (ranges
not provided).
In this analysis, the researchers
performed next-generation sequencing
to determine the prognostic impact of
common genomic alterations in MCL
(including TP53 mutations and deletions,
NOTCH1 mutations, CDKN2A dele-
tions, and WHSC1 mutations), and the
established prognostic indicators MCL
International Prognostic Index (MIPI)
score, Ki67 expression, and blastoid
morphology.
CDKN2A deletions were the
most commonly detected mutations
(n=35/177; 20%), followed by TP53
deletions (n=29/176; 16%). Twenty
patients had TP53 mutations, and nine
patients carried both TP53 mutations
and deletions.
In univariate analyses, TP53 dele-
tions, CDKN2A deletions, TP53 muta-
tions, and NOTCH1 mutations were each
significantly associated with poorer out-
comes. However, in multivariate analyses