CLINICAL NEWS
Effectiveness of Treatment with VR-CAP Versus R-CHOP for
Patients with Non-GCB DLBCL
Clinical outcomes differ considerably between the germinal center
B-cell-like (GCB) and non-GCB
subtypes of diffuse large B-cell
lymphoma (DLBCL), with overall
survival inferior in non-GCB patients. While R-CHOP (rituximab,
cyclophosphamide, doxorubicin,
vincristine, and prednisone) is the
standard frontline treatment for
DLBCL, outcomes with R-CHOP
are not as good in non-GCB
DLBCL compared with GCB, and
new approaches are needed for the
non-GCB group.
This study
highlights the
need for better identification of markers of poor
prognosis in
DLBCL and of
patients who
could achieve
better outcomes with
bortezomib.
The proteasome inhibitor
bortezomib has clinical activity in
patients with DLBCL, and earlier
studies suggested that bortezomib
may have specific utility in nonGCB DLBCL subtype. However,
according to results from the
phase II LYM-2034 trial, substituting bortezomib for vincristine
in the standard frontline treatment of R-CHOP did not improve
response or survival rates for
patients with non-GCB DLBCL.
“More efficacious therapies
targeting the molecular basis of
non-GCB DLBCL are required,”
wrote Prof. Fritz Offner, from the
University Hospital Ghent in Belgium, and colleagues in their report
recently published in Blood. “[The
results from] this study highlight
ASHClinicalNews.org
the need for better identification
of markers of poor prognosis in
DLBCL and of markers for patients
who could achieve better outcomes
with bortezomib-based therapy
versus standard R-CHOP.”
LYM-2034 was a phase
II, open-label, multinational,
randomized study to determine
if bortezomib plus R-CHOP
produces a clinical benefit in
patients with previously untreated
non-GCB DLBCL. The study was
conducted at 57 centers in 18
countries between January 2010
and December 2011. All 164 study
participants had immunohistochemistry-confirmed stage 2-4
disease or stage 1 primary mediastinal DLBCL.
Patients were excluded from
the study if they had a diagnosis of
transformed lymphoma (follicular,
T-cell, or Hodgkin lymphoma) or
central nervous system lymphoma;
previous chemotherapy or extended radiotherapy for lymphoma;
grade ≥2 peripheral neuropathy;
and uncontrolled or severe cardiovascular disease.
All study participants received
six 21-day cycles of R-CHOP
(rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, and doxorubicin 50 mg/m2 all delivered
intravenously on day one, followed
by prednisone 100 mg/m2 on days
one through five), and then were
randomized 1:1 to receive either:
• bortezomib 1.3 mg/m2 IV on
days one, four, eight, and 11
(VR-CAP treatment; n=84)
TABLE 2.
• vincristine 1.4 mg/m2 IV on day
one (R-CHOP treatment; n=80)
Treatment was discontinued
for progressive disease (PD) or
relapse, unacceptable toxicity,
patient withdrawal, and a delay
in treatment due to insufficient
recovery from toxicity of longer
than three weeks. Response and
PD were assessed at the end of
treatment cycles three and six, and
thereafter as clinically indicated.
Over a median follow-up of
24.9 months (range, 0-40 months),
the researchers found no significant difference in complete
response rate (CRR; the study’s
primary endpoint) between the
two groups: 64.5 percent for
VR-CAP and 66.2 percent for
R-CHOP (odds ratio [OR] = 0.91;
p=0.80). Similarly, no difference
was recorded for the secondary
endpoints of overall response rate
(93.4% for VR-CAP and 48.6% for
R-CHOP; OR = 0.21; p=0.11), progression-free survival (HR=1.12;
p=0.76), or overall survival
(HR=0.89; p=0.75) (TABLE).
Twenty-three (27%) patients in
the VR-CAP arm and 19 (24%) in
the R-CHOP arm received subsequent treatment; nine patients in
the VR-CAP arm and four in the
R-CHOP arm went on to receive
high-dose therapy and autologous
stem cell transplantation (HDTASCT) as subsequent therapy.
“At the time of this final
analysis, PFS and OS data had not
reached full maturity,” Prof. Offner
and colleagues wrote, “however,
findings from a recent report indicate that two-year PFS is a good
surrogate marker for long-term
outcomes in DLBCL, and therefore more extended follow-up is
unlikely to reveal a survival benefit
for VR-CAP.”
On the safety side, the rates
of adverse events (AEs) were
similar between the VR-CAP and
R-CHOP cohorts:
• Grade ≥3 AEs: 88% and 89%
• Serious AEs: 38% and 34%
• Discontinuations due to AEs:
7% and 3%
• Deaths due to AEs: 2% and 5%
However, grade ≥3 febrile neutropenia rates were lower, and grade
≥3 thrombocytopenia rates were
higher, with VR-CAP – likely
reflecting the different regimen
components, the authors added.
Prof. Offner and co-authors
note that the delay in treatment
caused by the central pathology
review procedure (albeit only
5 days on average) may have
excluded patients with the worst
disease prognosis from being
considered for participation in
the trial, “which may explain the
relatively good outcomes in both
arms of the study.”
REFERENCE
Offner F, Samoilova O, Osmanov E, et al. Frontline
rituximab, cyclophosphamide, doxorubicin, and
prednisone with bortezomib (VR-CAP) or vincristine
(R-CHOP) for non-GCB DLBCL. Blood. 2015 July 31. [Epub
ahead of print]
Rates of PFS, OS, and Patients Remaining Treatment-Free
Outcome, %
(95% CI)
VR-CAP
(n=84)
R-CHOP
(n=80)
80%
(69.0-87.5)
82.%
(71.4-89.3)
76.2
(64.2-84.7)
77.1%
(65.1-85.4)
One-year rate
91.2%
(82.3-95.7)
85.9%
(76.0-92.0)
Two-year rate
80.1%
(69.0-87.5)
79.0%
(67.9-86.6)
One-year rate
70.6%
(59.2-79.4)
78.4%
(67.2-86.2)
Two-year rate
69.3%
(57.8-78.3)
71.8%
(59.6-80.9)
Hazard Ratio
(95% CI)
p Value
PFS Rate
One-year rate
Two-year rate
1.12
(0.57-2.20)
0.76
0.89
(0.44-1.81)
0.75
OS Rate
Treatme