Literature Scan
event-free survival (EFS). Events
were defined as absence of complete
response (CR) or unconfirmed CR at
the end of all protocol treatment, or
relapse or death after previous CR or
unconfirmed CR.
Most patients (n=180/199; 90%)
received both cycles of MBVP or R-
MBVP. A total of 161 patients (81%)
went on to receive high-dose cytara-
bine consolidation per study protocol,
and 70 (35%) received whole-brain
radiotherapy (34 in the MBVP group
and 36 in the R-MBVP group).
The median follow-up in the study
was 32.9 months (IQR = 23.9-51.5
months). After one year, 98 patients
experienced an event: 51 in the MBVP
group and 47 in the R-MBVP group.
Of those patients, 79 died: 41 in the
MBVP group and 38 in the R-MBVP
group.
This translated to one-year EFS
rates of 49% in the MBVP group
and 52% in the R-MBVP group
(hazard ratio = 1.00; 95% CI 0.70-
1.43; p=0.99). The authors found no
significant difference in one-year
EFS rates after adjusting for age and
performance status.
Median EFS was 10.8 months
(range = 5.9-26.3 months) in the
MBVP group and 14.9 months (range
TABLE 1.
Progression-Free and Overall Survival Rates
MBVP (n=100) R-MBVP (n=99) Hazard Ratio p Value
One-year progression-free survival 41 (41%) 34 (34%) 0.77 (0.52-1.13) 0.18
One-year overall survival 79 (79%) 79 (79%) 0.93 (0.59-1.44) 0.74
= 7.0-41.4 months) in the R-MBVP
group. As seen in TABLE 1 , one-year
progression-free and overall survival
rates were similar between the two
groups.
Response rates also appeared simi-
lar in the MBVP and R-MBVP groups:
36% and 30%, respectively, achieved
a CR or unconfirmed CR following
induction chemotherapy, and this rate
improved to 53% and 45% after con-
solidation with high-dose cytarabine
(p value not provided). Radiotherapy
further improved CR and unconfirmed
CR rates in patients aged 60 or younger
(66% for MBVP and 68% for R-MBVP).
According to the authors, there was
“no evidence that treatment with R-
MBVP increased the number of CRs
or unconfirmed CRs compared with
MBVP (odds ratio = 1.08; 95% CI
0.59-1.98; p=0.81).”
Toxicity also was similar between
the two regimens, with 64% of MBVP-
treated patients and 58% of R-MBVP–
treated patients experiencing a grade
3 or 4 adverse event (AE). The most
common AEs in both groups included:
• infections (24% [MBVP] vs. 21%
[R-MBVP])
• hematologic toxicity (15%
[MBVP] vs. 12% [R-MBVP])
• CNS disorders (10% [MBVP]
vs. 15% [R-MBVP]; p values not
reported)
Similar proportions of patients in both
groups experienced life-threatening or
fatal serious AEs (12% in MBVP and
10% in R-MBVP). Treatment-related
death was observed in five patients in
the MBVP group and three patients
in the R-MBVP group. The authors
added that more patients receiving
R-MBVP stopped treatment due to ex-
cessive toxicity (5 in the MBVP group
and 11 in the R-MBVP group).
A possible explanation for the
lack of improvement with additional
rituximab is its inability to cross the
blood-brain barrier. The researchers
hypothesized that rituximab would
be able to penetrate this barrier while
it was disrupted due to whole-brain
radiotherapy, but that did not appear
to be the case. Results from a post hoc
subgroup analyses showed no differ-
ences in survival according to patient
sex or age, but the authors found a
statistically significant difference in
EFS favoring R-MBVP in patients
younger than age 60 (p=0.015). How-
ever, they noted, the study was not
powered for this comparison. Other
limitations include the study’s open-
label design.
The authors report relationships
with Roche.
REFERENCE
Bromberg JEC, Issa S, Bakunina K, et al. Rituximab in patients
with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a
randomised, open-label, phase 3 intergroup study. Lancet Oncol.
2019;20:216-28.
Is There a Role for AHCT Consolidation in MCL
in the Rituximab Era?
The availability of rituximab-
containing induction regimens for
patients with mantle cell lymphoma
(MCL) has improved outcomes, but
younger, transplant-eligible patients
may benefit from consolidative au-
tologous hematopoietic cell trans-
plantation (AHCT), according to
results from a retrospective analysis
published in the Journal of Clinical
Oncology. Investigators reported that
consolidative AHCT was associated
with longer progression-free survival
(PFS) compared with no AHCT,
while only a select group of patients
had improved overall survival (OS)
with AHCT consolidation.
“In most academic centers in the
U.S., the de facto standard of care for
young patients with newly diagnosed
MCL has been to treat with aggressive
induction therapy followed by con-
solidation with AHCT,” correspond-
ing author Stefan K. Barta, MD,
from the University of Pennsylvania,
told ASH Clinical News. However, he
noted, “this approach is based on an
earlier randomized study that was
36
ASH Clinical News
conducted before the rituximab era,
which showed an improvement in PFS
in patients consolidated with AHCT
after induction.”
With the present study, Dr. Barta
and colleagues retrospectively reviewed
outcomes for 1,029 younger patients
(≤65 years) who were transplant-
eligible at the time of MCL diagnosis
to assess the impact of consolidative
AHCT on survival. All participants
underwent and responded to induction
therapy between the years 2000 and
2015.
Patients’ median age was 57
years (range = 22-65 years), and the
authors noted that both the group
that underwent AHCT consolidation
and group that did not were balanced
regarding prognostic features, tumor
characteristics, and treatment mo-
dalities. The most common induction
regimens were intensive (e.g., hyper-
CVAD, maxi-CHOP, DHAP; 44%)
and CHOP-like (43%), followed by
bendamustine-based regimens (11%).
Nearly all patients (973; 95%) received
an anti-CD20 monoclonal antibody
with induction, and 306 (30%) re-
ceived maintenance rituximab.
A total of 657 patients (64%) un-
derwent AHCT consolidation within
six months of induction. Of the 372
patients who did not undergo AHCT,
reasons included physician choice
(67%), patient preference (18%), and
“other” (e.g., mobilization failure; 3%).
month to 17.1 years), respectively.
Median PFS was 75 months among
AHCT recipients, compared with 44
months among nonrecipients (hazard
ratio [HR] = 0.64; 95% CI 0.54-0.78;
p<0.01). In multivariate regression
analysis, AHCT was associated with
improved PFS (the study’s primary
endpoint; HR=0.54; 95% CI 0.44-0.66;
“[Our study] calls into question
whether all young and fit
patients with newly diagnosed
MCL need to receive an AHCT
post-induction.” —STEFAN K. BARTA, MD
After a median follow-up of 6.3
years (range = 1-205 months), the me-
dian PFS and OS for the entire cohort
were 62 months (range = 1 month to
17.1 years) and 138 months (range = 1
p<0.01), but the authors observed only
a statistical trend toward improvement
in OS (HR=0.77; 95% CI 0.98-1.01;
p=0.06).
This relationship also was noted
June 2019