Literature Scan
New and noteworthy research from the
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Greater Survival and Response Rates with
Bendamustine-Rituximab than FludarabineRituximab in Patients with Non-Hodgkin
Lymphoma and Mantle Cell Lymphoma
The combination of bendamustine
and rituximab (BR) resulted in
superior overall response rates
(ORR) and complete response
(CR) rates, as well as progressionfree survival (PFS) and overall
survival (OS), compared with the
combination of fludarabine plus
rituximab (FR) in patients with
relapsed, indolent non-Hodgkin
lymphoma (NHL) and mantle cell
lymphoma (MCL).
The randomized, open-label,
phase III study, by Prof. Matthias
Rummel, from the Department
of Hematology and Oncology
at the Justus-Lieig Universität
in Giessen, Germany, and colleagues, included 219 patients
from 55 centers in Germany enrolled between October 8, 2003,
and August 5, 2010.
“At the time of the design
and development, no standard
treatment approach had been
established for relapsed patients
with indolent lymphomas or
MCL who were ineligible for
stem cell transplant,” the authors
wrote, “making treatment decisions somewhat subjective.” As
patients who relapse are typically
older and have comorbidities,
tolerable treatments that provide
durable remissions and prolonged
survival are needed, they added.
The median patient age of the
study population was 67 years
(range = 59-74 years), with approximately one-third of patients
older than 70 years, “suggesting
that our patient population is representative of that typically noted
in clinical practice,” the author s
wrote. The median number of prior treatments was one, with most
patients having received cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone
(CHOP)-based chemotherapy.
All patients had stage 2 to 4
disease, a World Health Organization performance status of
26
ASH Clinical News
0 to 2, and one of the following
CD20-positive lymphoma entities
confirmed by a histology report:
• Follicular lymphoma (grade
1 and 2)
• Lymphoplasmacytic lymphoma (Waldenström macroglobulinemia)
• Small lymphocytic lymphoma
(SLL)
Overall and complete responses were significantly higher with
the bendamustine combination, as
well. See TABLE 1 for an additional
comparison of response rates
between treatment groups.
Prof. Rummel and colleagues
also stratified patients based on
histologic subtypes, finding that
patients with follicular lymphoma
who received BR experienced the
greatest increase in PFS compared
with FR treatment:
• Nodular and generalized
marginal zone lymphoma
• Follicular lymphoma: HR =
0.56 (95% CI 0.34-0.87)
• MCL
• MCL: HR=0.45 (95% CI
0.22-0.76)
Patients were excluded from the
study if they were refractory to
regimens that included rituximab, bendamustine, or purine
analogue drugs or had significant comorbidities.
Patients were randomized
to receive rituximab (375 mg/
m2 on day 1 of each cycle) with
either bendamustine (90 mg/
m2 administered as a 30-minute
infusion on days 1 and 2; n=114)
or fludarabine (25 mg/m2 on days
1-3; n=105).
PFS (the study’s primary endpoint) was assessed via clinical assessment every three months and
computed tomography scan and
sonographic examination every
six months until relapse.
After a median follow-up of 96
months, the median PFS was significantly higher in the BR-treated
cohort, compared with the FRtreated cohort: 34.2 months (95%
CI 23.5-52.7) versus 11.7 months
(95% CI 0.38-0.72; p<0.0001).
Patients in the BR cohort
also had longer median OS:
109.7 months (95% CI 50.2-not
reached) versus 49.1 months
(95% CI 36.2-59) in the FR
group (hazard ratio [HR] = 0.64;
95% CI 0.45-0.91; p=0.012).
• SLL sub-entities: HR=0.28
(95% CI 0.07-0.62)
The authors noted no differences
in adverse events (AEs) between
the BR and FR treatment groups.
The most common AEs in both
cohorts were infections (11 in the
BR group and 8 in the FR group)
and myelosuppression (3 and 2).
The study protocol was
amended in 2006, after the European Medicines Agency approved
rituximab maintenance therapy
for patients with relapsed FL, to
TABLE 1.
allow administration of rituximab
maintenance therapy for patients
who had responded to BR or FR
treatment.
“Our study showed a
survival benefit of one chemoimmunotherapy regimen over
another, and suggests that the
use of rituximab maintenance
potentially further improves
outcomes in the relapsed setting,”
Prof. Rummel told ASH Clinical
News. “The combination of BR
was once more confirmed to be
an effective and well-tolerated
treatment regimen.”
Of the 152 patients who
responded to either BR or FR,
44 patients received rituximab
maintenance with BR (n=25)
or FR (n=19) and 108 patients
did not (BR, n=69; FR, n=39).
Median PFS was longer among
the 44 patients who had received
maintenance rituximab therapy,
compared with those who did not:
72.1 months (95% CI 54.1 - not
reached) versus 30.4 months (95%
CI 24.7-36.5), for an HR of 0.52
(95% CI 0.37-0.86; p=0.01).
Similarly, median OS was
significantly increased in patients who received maintenance
rituximab therapy: not reached
(95% CI 93.6 - not reached) versus
Responses to Treatment in Each Cohort
Bendamustine
Plus Rituximab
Fludarabine
Plus Rituximab
Overall response
94
(82%)
54
(51%)
<0.0001
Complete response
46
(40%)
18
(17%)
0.0002
Partial response
48
(42%)
36
(34%)
0.2345
Stable disease
7
(6%)
16
(15%)
0.0282
Progressive disease
8
(7%)
30
(29%)
<0.0001
Not evaluable
5
(4%)
5
(5%)
0.8941
p value
June 2016