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 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 1927-1932
Rituximab (Anti-CD20 Monoclonal Antibody) for the Treatment of
Patients With Relapsing or Refractory Aggressive Lymphoma: A
Multicenter Phase II Study
By
B. Coiffier,
C. Haioun,
N. Ketterer,
A. Engert,
H. Tilly,
D. Ma,
P. Johnson,
A. Lister,
M. Feuring- Buske,
J.A. Radford,
R. Capdeville,
V. Diehl, and
F. Reyes
From the Service d'Hématologie, Centre Hospitalier Lyon-Sud,
Pierre-Bénite, France; the Service d'Hématologie,
Hôpital Henri-Mondor, Créteil, France; the Klinik 1 fur
Innere Medezin, Üniversität zu Köln, Köln,
Germany; the Service d'Hématologie, Centre Henri
Bécquerel, Rouen, France; the Department of Hematolgy, Royal
North Shore Hospital, St Leonards, Australia; the Cancer Research
Building, St James University Hospital, Leeds, UK; the Department of
Medical Oncology, St Bartholomew's Hospital, London, UK; the Zentrum
fur Innere Medizin, Abt. Hematologie und Onkologie, August
Universität, Göttingen, Germany; the CRC Department of
Medical Oncology, University of Manchester, Manchester, UK; and
Hoffman-La Roche, Basel, Switzerland.
 |
ABSTRACT |
Rituximab, a chimeric monoclonal antibody that binds specifically to
the CD20 antigen, induced objective responses in 50% of patients with
low-grade or follicular B-cell lymphoma. Because most nonfollicular
B-cell lymphomas also express the CD20 antigen, we conducted a phase II
study to evaluate the efficacy and tolerability of this new agent in
patients with more aggressive types of lymphoma. Patients with diffuse
large B-cell lymphoma (DLCL), mantle cell lymphoma (MCL), or other
intermediate- or high-grade B-cell lymphomas according to the Working
Formulation were included in this prospective randomized phase II study
if they were in first or second relapse, if they were refractory to
initial therapy, if they progressed after a partial response to initial
therapy, or if they were elderly (age >60 years) and not previously
treated. The patients received 8 weekly infusions of rituximab at the
dose of 375 mg/m2 in arm A or one infusion of 375 mg/m2 followed by 7 weekly infusions of 500 mg/m2 in arm B. Patients were evaluated 2 months after the
last rituximab infusion. Fifty-four patients were randomized from 9 centers in Europe and Australia (28 in arm A and 26 in arm B). A total
of 5 complete responses (CR) and 12 partial responses (PR) were
observed among the 54 enrolled patients, with no difference between the two doses. In an intent-to-treat analysis, the CR rate was 9% (CI95%, 3% to 20%) and the PR rate was 22%
(CI95%, 12% to 36%), for an overall response rate of
31% (CI95%, 20% to 46%). An analysis of prognostic
factors showed that response rates were lower in patients with
refractory disease, patients with lymphoma not classified as DLCL, and
patients with a tumor larger than 5 cm in diameter. DLCL and MCL
patients had response rates of 37% and 33%, respectively. The median
time to progression exceeded 246 days for the 17 responding patients.
The most frequently reported adverse events were related to an infusion
syndrome and were mild: 19% of the patients had a grade 3 related
adverse event, slightly more in arm B, and only 1 patient had a grade 4 related adverse event in arm A. Two patients (3.7%)
withdrew from treatment because of severe adverse events, one patient
in each arm. In this first trial of rituximab in DLCL and MCL, patients
experienced a significant clinical activity with a low toxicity.
Rituximab has significant activity in DLCL and MCL patients and should
be tested in combination with chemotherapy in such patients.
© 1998 by The American Society of Hematology.
| |
INTRODUCTION |
RITUXIMAB IS A chimeric anti-CD20
monoclonal antibody containing human IgG1 and  constant regions with
murine variable regions.1 The antilymphoma effects of
rituximab are probably due to complement and antibody-dependent
cell-mediated cytoxicity,2 inhibition of cell
proliferation, and induction of apoptosis.3 In phase I
studies, rituximab induced a rapid depletion of CD20+
normal B cells and lymphoma cells.1 Phase I trials of
single doses up to 500 mg/m2 and of four weekly doses of
375 mg/m2 demonstrated clinical responses with no
dose-limiting toxicity in low-grade or follicular lymphoma
patients.4 In a phase II trial, four weekly infusions of
375 mg/m2 induced responses in 17 (50%) of 34 evaluable
low-grade or follicular lymphoma patients, with a median time to
progression of 10.2 months.5 Side effects were associated
with the first rituximab infusion and usually were mild to moderate. In
a recently reported large pivotal phase II study in 166 patients with
low-grade or follicular lymphoma, objective response was reported for
76 (50%) of 151 evaluable patients and side effects were identical to
those previously described.6 Previous experience with
rituximab in patients with large B-cell lymphoma is very limited, with
fewer than 12 patients having been included in the early phase I-II
studies. However, nonfollicular B-cell lymphoma cells resemble
follicular or small lymphocytic lymphoma cells in their expression of
the target CD20 antigen and therefore may also respond to rituximab therapy.
We designed this phase II trial in patients with aggressive
B-cell lymphomas, ie, intermediate- and high-grade lymphomas according to the Working Formulation, to evaluate the clinical efficacy and
toxicity of rituximab monotherapy in these patients.
| |
MATERIALS AND METHODS |
Patients.
Patients were eligible for inclusion in this study if they had
intermediate- or high- grade non-Hodgkin's lymphoma (NHL) according to
the Working Formulation,7 subtypes D to H. Patients were required to have progressive disease either after one or two prior chemotherapy regimens or were more than 60 years of age without any
prior therapy. Confirmation that the lymphoma cells expressed CD20
antigen was required, as was the presence of measurable disease in at
least one site not previously irradiated. Bone lesions, ascites, and
pleural effusions were not considered measurable. Patients were
required to be more than 18 years of age, ambulatory (Karnosfky score
 70%), and must have given written informed consent. Patients were
not included if they had other NHL subtypes, had a total doxorubicin
dose greater than 400 mg/m2, had prior radioimmunotherapy
for this lymphoma, had a history of other cancer, had major surgery 4 weeks before the study, had clinically significant cardiac disease or
myocardial infarction during the 6 months before the study, had
abnormal liver or renal functions not related to lymphoma, had active
opportunistic infection, had human immunodeficiency virus
(HIV)-positive serology, were HBsAg positive, or had HBc or HCV
antibodies. The study was conducted according to the
principles of the Declaration of Helsinki and had been approved by the
local Institutional Review Boards or Ethics Review Committees according
to local regulations.
Study design.
The study was an open-label, randomized, phase II trial to evaluate the
clinical efficacy of rituximab, as defined by the response rate, and
safety. Patients were randomized to receive weekly intravenous doses of
rituximab at either regimen A (375 mg/m2 once weekly for 8 weeks) or regimen B (375 mg/m2 on day 1 followed on day 8 by 500 mg/m2 once weekly for 7 weeks). These two doses were
chosen because the dose of 375 mg/m2 was the dose found to
be effective and well tolerated in patients with indolent
NHL,4 whereas the dose of 500 mg/m2 was the
highest dose tested in phase I trials.1 Patients were allocated to treatment groups by a central randomization. The randomization was stratified between previously treated and previously untreated patients. Rituximab was administered intravenously in an
outpatient setting through a peripheral or central intravenous line.
Infusion was started at an initial rate of 50 mg/h. If no toxicity was
observed during the first hour, the dose rate was escalated by
increments of 50 mg/h every 30 minutes to a maximum of 300 mg/h. If the
starting dose of rituximab was well tolerated, the starting flow rate
for the administration of the second and subsequent infusions was fixed
at 100 mg/h with similar increments at 30 minute intervals up to 400 mg/h. The infusion was interrupted if severe fever, rigors, edema or
mucosa congestion, hypotension, or any other serious adverse events
occurred. After the events resolved, the infusion was to be resumed at
half the previous rate. The dose was not modified throughout the
treatment period. It was recommended that patients at risk of tumor
lysis syndrome receive appropriate hydration and allopurinol (300 mg/d). Treatment with corticosteroids or other chemotherapeutic agents
was not permitted. Administration of oral premedication with
acetaminophen at 1,000 mg and diphenhydramine hydrochloride at 50 to
100 mg was recommended 30 to 60 minutes before each infusion.
Evaluation of the tumor burden and involved sites was performed before
treatment, at weeks 5 (before the fifth dose of rituximab), 9 (end of
the treatment), 12, and 16 to evaluate the treatment efficacy and its
persistence 2 months after the end of treatment. Patients with
progressive disease (PD) during or after treatment were taken off the
study. Patients with stable disease (SD) at the end of treatment (week
9) were also taken off the study and were permitted alternative
treatment at the discretion of their local physician. Patients
achieving a partial response (PR) or complete remission (CR) were
followed-up until week 16 and were then allowed to go off study and to
receive further treatment at the discretion of their local physician.
Safety assessments were performed for all patients for a minimum of 8 weeks after the last infusion of rituximab. Adverse events were graded
according to the World Health Organization score.
Endpoints.
The primary efficacy endpoint was the objective response rate, ie, the
proportion of patients achieving either a CR or a PR at any time during
the study. Response was assessed by the investigator, using the
standard World Health Organization criteria, and confirmed by the
sponsor based on reported tumor dimensions at each assessment. PR was
defined as a decrease equal to or greater than 50% in the sum of the
products of perpendicular diameters for each target lesion (SPD). CR
was defined as the disappearance of all lesions, but the presence of
residual lymph nodes measuring less than 1 × 1 cm on computer
tomography (CT) scans was regarded as consistent with an
assessment of CR. A PD was defined as any occurrence of a new lesion or
an increase of 25% or more in the size (product of perpindicular
diameters) of any target lesion. A SD was defined as no change in SPD
or a change not corresponding to PR or PD. Secondary efficacy
parameters were time to response and time to progression. Time to
response was defined as the time from the first infusion to the date of
the maximum response. Time to progression (TTP) was defined as the time
from the first infusion to the date of disease progression. Patients
receiving any other treatment at the end of the study were considered
to be in PD at the time of this new therapy for purposes of this
analysis. Patients with no report of PD or further therapy were
censored from the analysis of TTP as of their off-study date or the
date of last progression-free follow-up, whichever was the earliest.
This study was designed with a short follow-up (8 weeks after the
treatment for a total of 16 weeks) to allow all patients, regardless
their response status, to receive further therapy at their physician's
discretion. Thus, the trial was only designed to evaluate tumor
response, rather than time-dependent variables such as TTP or response
duration. However, available data for TTP and response duration are
presented here to provide an estimate of the extent of patient benefit
resulting from rituximab therapy.
Response rates with 95% confidence intervals (CI) are reported as an
intent-to-treat analysis. TTP and corresponding 95% confidence limit
estimates were computed using the standard Kaplan-Meier method of the
SAS lifetest procedure. The planned sample size was adequate to
determine, with 95% confidence, whether the true response rate was
equal to or greater than 30%.
| |
RESULTS |
Patient characteristics.
Fifty-four patients were enrolled in the study from 9 centers in a
6-month period (September 1996 to March 1997). One patient randomized
to group B received treatment A and has therefore been analyzed as part
of group A, leaving 28 patients in arm A (350 mg/m2) and 26 patients in arm B (350 mg/m2, then 500 mg/m2).
The characteristics of these patients at the time of their entry in the
study as well as their prior lymphoma history are presented in
Table 1. Thirty patients (56%) had diffuse
large B-cell lymphoma (DLCL) according to the REAL
Classification8 and 13 patients (24%) had a mantle cell
lymphoma (MCL). One patient had a follicular large-cell lymphoma. The
disease could not be precisely categorized in the REAL classification
for the other 10 patients, but these patients were classified as
intermediate grade in the Working Formulation (6 patients with subtype
G and 4 with subtype H). Only 9 patients (17%) were previously
untreated, 17 (31%) were in first relapse, 5 (9%) in second relapse,
and 23 patients (43%) were in progressive disease after failure or partial response to their first chemotherapy regimen. Nine (17%) enrolled patients had been treated with intensive therapy and autologous stem cell transplantation (ABMT). Demographic and disease characteristics were well balanced between the two groups, except for a
slight excess of patients in second relapse or who had received ABMT in
group A and for a slight excess of MCL in group B.
Treatment and response rate.
Eighteen patients (33%) did not complete the 8-week treatment course
(10 in group A and 8 in group B) due to PD in 14 (26%) patients (8 in
arm A and 6 in arm B); adverse events in 2 (4%) patients (1 in each
arm); personal reasons in 1 patient; and investigator judgement in 1 patient. Thirty-six patients (67%) completed the 8-week treatment, 14 of them being withdrawn from the study before the last scheduled visit
at week 16 (7 in arm A and 7 in arm B). Eight of these 14 withdrawn
patients had PD (5 in arm A and 3 in arm B); 4 had stable disease (2 in
each arm); and the reason was investigator judgement in 1 patient and
loss of follow-up in 1 patient. This last patient had PD later, after
week 16. The median time to progression in these patients was 4 weeks
(range, 4 to 56 days). Twenty-two patients (41%), 11 in arm A (39%)
and 11 in arm B (42%), completed the study at the last visit of week 16.
Tumor response was assessed by the investigator and was reassessed and
confirmed by the sponsor. Two patients were not evaluable for response:
1 patient was taken off study immediately after the first infusion
because of an adverse event and 1 patient did not have a CT scan
performed at baseline and had lung localization at the CT scan
performed after week 4. This patient had a PR in all baseline sites.
According to the sponsor's confirmatory assessment, there were 5 CR (4 in arm A and 1 in arm B) and 12 PR (5 in arm A and 7 in arm B).
Although there were slightly more CRs in arm A than in arm B, the
overall response rate was not statistically significantly different
between the two groups (32% and 31% in the intent-to-treat
analysis for arms A and B, respectively). Therefore, a pooled analysis
of both groups was performed. The overall response rate was 31%
(CI95%, 20% to 46%) in the intent-to-treat analysis and
33% (CI95%, 20% to 47%) for the 52 evaluable patients
(Table 2).
Despite a dramatic initial tumor shrinkage, some patients achieved
their best response late in the course of the study
(Fig 1). The median time to response was 56 days, ranging from 18 to 115 days. The median time to response was
slightly shorter in arm B (41.5 days; range, 18 to 90 days) than in arm
A (80 days; range, 27 to 115 days).
Parameters associated with response.
In an attempt to identify factors associated with favorable response,
an analysis was performed to correlate response rates with patient
characteristics at the time of the study and with patients' prior
lymphoma history (Table 3). Patients with
DLCL had a 37% response rate and those with MCL had a 33% response rate. Only 1 of the 9 evaluable patients with a lymphoma not
reclassified in the REAL classification responded and reached a CR. The
other 8 patients had a G or H subtype (4 in each group). This
difference is not statistically significant when compared with DLCL and
MCL entity (P > .2). Prior lymphoma history influenced the
response: patients with no prior treatment and those in first or second relapse were more likely to respond to rituximab, with response rates
of 33%, 41%, and 80%, respectively. All patients who achieved a
complete response were in their first or second relapse with a CR rate
and an overall response rate for relapsing patients of 23% and 50%,
respectively. In contrast, the response rate was 22% in patients with
primary refractory disease and 8% in those who progressed after a PR
to their initial treatment. However, these lower response rates were
not statistically significantly different from those of relapsing
patients, probably because of the low number of patients in this study.
Interestingly, patients previously treated with intensive therapy and
ABMT did not have a lower response rate. Tumor burden (as defined by
the largest diameter of the largest lesion) at the time of rituximab
treatment influenced the response: patients whose largest tumor was
less than 5 cm in diameter were more likely to respond (46%) than
patients whose largest tumor was greater than 5 cm (17%). No responses were observed in patients whose largest tumor was greater than 10 cm in
diameter.
Duration of response.
A long-term follow-up beyond the visit scheduled at week 16 was not
planned in the protocol, and patients' management after the off-study
date varied substantially between centers. Consequently, the definition
of time to progression was defined conservatively by the date of either
a recorded disease progression or an investigator's decision to begin
a new treatment. Only 6 of the 17 responding patients (35%) had
progressed at the time of analysis with a progression occurring between
day 83 and day 246 after the first rituximab infusion. Because most
patients had not progressed and because progression was imputed rather
than observed for patients who received further treatment, the
conclusion of the TTP analysis is limited to the statement that the
median TTP for patients in arm A and arm B exceeded 105 days and 121 days, respectively. When both groups were pooled, the median TTP of the
54 patients enrolled in the study exceeded 105 days (range, 0 to 336+
days). The median TTP for the 17 responding patients exceeded 246 days (range, 83 to 336+ days).
Toxicity.
All patients enrolled in this study received at least 1 infusion of
rituximab. Eighteen patients in each arm received the 8 infusions
planned in the protocol. The mean total infusion time for the first
infusion was approximately 5 hours for patients in both arms, ranging
from 0.5 to 10.1 hours. Thereafter, the infusion time decreased in both
arms, being slightly longer in arm B (3.7 to 4.5 hours compared with
3.1 to 3.3 hours in arm A). The number of patients requiring an
interruption, a slowing of the infusion rate, or a discontinuation was
slightly higher in arm B than in arm A (6, 2, and 1, respectively, for
arm A patients compared with 14, 4, and 5, respectively, for arm B
patients).
A summary of all adverse events (AE) reported during treatment probably
or possibly related to rituximab or with unknown relationship is listed
in Table 4. Two and 3 patients did not
experience any AE in arm A and arm B, respectively. Altogether, 26 patients experienced 125 AE in arm A and 23 patients experienced 143 AE
in arm B. The majority of these events (90% in arm A and 86% in arm
B) were of mild to moderate severity. Nine patients (29%) experienced 13 grade 3 or 4 AE in arm A and 9 patients (35%) experienced 20 grade
3 or 4 AE in arm B. The most frequent AE in both groups were in the
body as a whole body system. These AE were fever, rigors, hypothermia,
and edema. Mild to moderate hypotension was reported in 6 patients
(21%) and 3 patients (11%) in arms A and B, respectively. Hypotension
was severe only in 1 patient in arm B. The most frequent respiratory AE
were dyspnea (21% and 8% of patients in arms A and B, respectively)
and coughing (11% in both arms). AE involving the skin were
principally increased sweating (18% and 19% of patients in arm A and
B, respectively) and pruritus (11% in both arms). In both arms, the
majority of AE occurred during or after the first infusion
(Fig 2). The frequency of adverse events
and their severity decreased for the subsequent infusions. However,
more patients in arm B than in arm A experienced AE from the second
infusion onwards (Fig 2). Grade 3 and grade 4 AE were predominantly
seen during or shortly after the first infusion. Two deaths during the
study period were reported, both in arm B, and both were judged to be
secondary to the study disease. Before death, both patients had been
taken off the study because of progressive disease.
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Table 4.
Adverse Events Reported During the Trial Period Possibly
or Probably Related to Rituximab or With Unknown Relationship
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Fifteen patients experienced a serious AE, 7 (25%) in arm A and 8 (31%) in arm B. When considering the events judged to be related to
treatment with rituximab, 3 and 11 events were reported for 3 (11%)
and 6 (23%) of patients in arms A and B, respectively. All patients
recovered from these AE. Only 2 patients stopped treatment because of a
drug-related AE: 1 patient in arm A presented an anaphylactic shock
after the first infusion; 1 patient in arm B presented severe rash,
arthralgia, fever, and thrombocytopenia after the second infusion. Both
patients recovered from the AE. Severe neutropenia was observed in only
1 and 3 patients in arms A and B, respectively. Severe thrombocytopenia
was observed in 3 patients in arm B but not in arm A. Severe anemia was
reported in only 1 patient in arm A. The most frequent hematologic AE
was lymphocytopenia, which was severe in 17 (61%) and 21 (81%)
patients in arms A and B, respectively. However, it was present at
baseline in the majority of these patients.
An infection was defined as any occurrence of an AE suggestive of an
infection and/or any occurrence of therapeutic use of anti-infectious drugs (antibiotics, antivirals, and antifungals). Infections were classified as bacterial, viral, fungal, or unknown. An
episode of infection was recorded in 39% and 31% of patients in arms
A and B, respectively (Table 5). Five
patients experienced a respiratory infection (bronchitis, pneumonitis,
pneumonia, and febrile pleural effusion), 2 patients had pharyngitis,
and 3 patients had rhinitis. Urinary tract infection occurred in 5 patients, an abscess in 2, and a flu-like syndrome in 2. Conjunctivitis, gastroenteritis, herpes simplex infection,
Escherichia coli septicemia, candida mucositis, and arthritis
occurred in 1 patient each. Only 10 episodes were thought to be related
to rituximab, none of them being serious or related to opportunistic
pathogens and the remainder being described as related to either
concomitant disease or to study disease.
CD20+ B cells were rapidly depleted from circulating blood
for most patients after three infusions of rituximab. CD20+
cells remained below normal limits until week 16. The mean serum IgG,
IgA, and IgM levels remained within normal range throughout the study.
| |
DISCUSSION |
This study is the first trial intended to evaluate the efficacy and the
safety of an anti-CD20 monoclonal antibody therapy in patients with
aggressive lymphoma (defined as the intermediate- and high-grade
subtypes of the Working Formulation). The study was designed to
evaluate the safety of two dosing regimens of rituximab and to define
whether the true response rate was equal to or greater than 30%.
The patients' baseline characteristics were well balanced between the
two groups. The dominant features of this population were a relatively
old age, as compared with the published literature, and a high
proportion of previously treated patients. These characteristics were
expected because young patients in either refractory or relapsing disease stage are usually treated with intensive therapy and ABMT. Thus, only patients who had declined or who were too old for high-dose therapy were included in this trial.
There were no major differences in the response rates between the two
treatment groups. The overall response rate was 31% in the
intent-to-treat population of 54 patients and 32% with a 10% CR rate
in the evaluable patients (n = 52). This response rate is above the
minimal desirable threshold that was defined by the protocol and is
similar to what would be expected with single-agent therapy in this
patient population. In contrast, it is below the response rate usually
obtained with combination chemotherapy such as the DHAP,9
ESHAP,10 or VIM11 regimens used in this
setting. These types of regimens are often used in younger patients and
have been associated with a much higher toxicity, particularly
hematologic toxicity. Therefore, a direct comparison of the merits of
rituximab monotherapy versus combination chemotherapy is not considered
appropriate. In addition, such a comparison would be limited by the
fact that elderly patients are commonly excluded or underrepresented in
published trials. In our study, 50% and 62% of patients enrolled were
older than 60 years of age in arms A and B, respectively. Additionally,
comparison of any single agent administered for 8 weeks and
intensive, high- dose chemotherapy regimens administered over several
months is not appropriate.
The estimated time-to-progression exceeded 105 days and 246 days for
the whole population and for the responding patients, respectively.
Taking into account that patients in this study were refractory or
relapsed and that these results were achieved with a biological
therapy, these data should be viewed at least as encouraging. Some
patients reached long-lasting progression-free intervals up to 11+
months. The results of this study suggest that the factors that may be
associated with a higher likelihood of response are a relapsed or
previously untreated disease, a histology of DLCL, a low tumor burden,
and a good performance status. Interestingly, a reasonably high
response rate was associated with MCL, an entity known to be refractory
to chemotherapy.
Importantly, these results were obtained without the characteristic
toxicity of combination chemotherapy regimens and over a shorter
treatment period. Even if a majority of patients experienced events
thought to be related to rituximab, only 2 patients (4%) were
withdrawn from the study because of adverse events and no toxic deaths
were observed. Most of the adverse events were mild to moderate in
severity (Fig 2). As previously described in trials in patients with
low-grade or follicular lymphoma, most adverse events occurred during
or after the first infusion of rituximab, and the number and the
severity of adverse events decreased with the subsequent infusions. The
most frequent AE were events usually described under the term of
infusion-related syndrome, such as fever, chills, rigors, mild to
moderate hypotension, and headache. Two serious adverse events reported
in this study were not previously described in the earlier trials with
rituximab. First, a patient experienced serum sickness that occurred
after the second infusion and recovered with corticosteroid treatment.
Second, a patient suffered from a severe hypotension and bronchospasm
(described as anaphylactic shock) during his first infusion, which
prompted his withdrawal from the study.
The very low incidence of cytopenia is a clinically significant
difference from the toxicity usually associated with combination chemotherapy regimens. Only 4% and 8% of patients experienced severe
neutropenia in arms A and B, respectively. Similarly, severe thrombocytopenia was not reported for any patient in arm A and for 12%
of patients in arm B. The frequency of grade 3 and grade 4 adverse
events (23%) and of serious adverse events (23%) was higher in arm B
treatment than in arm A (18% and 16%, respectively). Patients in arm
B required more infusion alterations due to these adverse events. These
results indicate that the higher dose of rituximab was slightly less
well tolerated than the standard dose of 375 mg/m2. The
infectious episodes were not different between the two doses (Table 5)
but were slightly more frequent than in the previous reports in
low-grade lymphomas.4,5 However, the episodes qualified as
related to rituximab treatment by the investigators were not
statistically different. It is thus difficult to incriminate the longer
duration of the treatment as responsible for this slow increase in
infectious rate.
In conclusion, the results of this study indicate that rituximab
therapy has significant anti-lymphoma activity in DLCL and MCL patients
without the toxicity commonly observed with combination chemotherapy
regimens. There was no marked differences in efficacy between the two
dosing regimens, but the safety profile of the higher dose (500 mg/m2) was less favorable as compared with the standard
dose regimen (375 mg/m2). This regimen should be evaluated
in combination with standard chemotherapy in patients with aggressive
B-cell lymphoma.
| |
FOOTNOTES |
Submitted February 24, 1998;
accepted May 13, 1998.
Address reprint requests to B. Coiffier, MD, Service
d'Hématologie, Centre Hospitalier Lyon-Sud, 69495 Pierre-Bénite Cedex, France; e-mail:
coiffier{at}hematologie.univ-lyon1.fr.
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" is accordance with 18 U.S.C. section 1734 solely to indicate this fact.
| |
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Abstract
Introduction
Abstract
