rituximab (Rituxan) to standard chemotherapy
for follicular lymphoma
regimens improves the rate and quality
of responses and increases clearance
of the bcl-2/IgH chimeric gene,
according to studies from US and
Italian cooperative groups reported
at the 43rd Annual Meeting of the
American Society of Hematology.
David G. Maloney, MD, PhD, reported
on behalf of the Southwest
Oncology Group (SWOG) that treating
advanced-stage follicular lymphoma
with a cycle of rituximab after
standard CHOP (cyclophosphamide
[Cytoxan, Neosar], doxorubicin
HCl, vincristine [Oncovin], prednisone)
significantly improved the
quality of responses in 19% of patients,
and brought the complete response
rate to 54% (abstract 3502).
Pier Luigi Zinzani, MD, PhD, reported
on behalf of the Italian Cooperative
Study Group on Lymphoma
that adding rituximab to either
FM (fludarabine [Fludara],
mitoxantrone [Novantrone]) or
CHOP improved both the molecular
clearance rate and the quality of
responses in patients with follicular
lymphoma (abstract 3500).
Dr. Maloney, an associate member
at the Fred Hutchinson Cancer
Research Center in Seattle, reported
data from the SWOG-9800 trial.
"There is currently no consensus on
what should be first-line therapy for
advanced follicular non-Hodgkin's
lymphoma (NHL)," Dr. Maloney
said. "Combination chemotherapy
usually induces remissions, but nearly
all patients eventually progress and
there is no clear plateau on diseasefree
Dr. Maloney reported that SWOG
designed a major study of CHOP plus
rituximab because CHOP produces
a high response rate, and rituximab
is effective in patients with nonbulky
disease and has activity in relapsed
disease. "Single-agent treatment with
rituximab induces response rates of
approximately 50% to 60% in patients
with relapsed follicular NHL.
In some patients, the molecular detection
of disease by polymerase chain
reaction (PCR) assay may be eliminated
following antibody therapy,"
End Points Include Safety and
The SWOG study objectives were
to evaluate safety and to determine
2-year failure-free survival and the
rate of disappearance of clonal bcl-2
oncogene rearrangements from the
peripheral blood and bone marrow
following CHOP and rituximab.
The study included 104 patients
from 49 institutions. The median
age was 53 years (range: 27 to 76);
54% were male; and 10% had bulky
stage II, 34% stage III, and 57% stage
IV disease. Thirty percent had B
symptoms and 31% had bulky disease.
Eighty-five were eligible for and
treated with six cycles of standard
CHOP (cyclophosphamide at 750
mg/m2, doxorubicin at 50 mg/m2,
vincristine at 1.4 mg/m2, and prednisone
at 100 mg orally for 5 days),
given at 3-week intervals. Following
CHOP chemotherapy, one patient
died of infection. Grade 4 toxicities
included 25 hematologic events, 1
cardiovascular, 1 gastrointestinal,
and 1 unknown.
Patients were restaged 4 weeks
following the sixth cycle of CHOP,
and those who had either a partial
(PR) or complete remission (CR)
were eligible for rituximab. This included
74 patients, one of whom
refused treatment. The remaining 73
patients were given four doses of
rituximab at 375 mg/m2 each week.
Following rituximab, 1 patient had
grade 4 neutropenia and 12 had
grade 3 toxicity.
Response-Relapses an Issue
Dr. Maloney reported response
data for 84 patients (see Table 1).
Fifty-four percent had a confirmed
or unconfirmed CR, and 18% a PR,
for an overall response rate of 72%.
Rituximab improved responses in
16 patients (19%), converting PR to
CR in 14 patients, stable disease to
CR in 1 patient, and unconfirmed
CR to confirmed CR in 1 patient.
The 2-year progression-free survival
rate was 74%, and the 2-year overall
survival rate was 95%.
"This regimen is well tolerated
and overall survival is excellent, but
despite the improvement in the CR
rate, there continue to be relapses in
these patients similar to what would
be expected with chemotherapy
alone," Dr. Maloney said.
To further address this problem,
he said that SWOG is conducting a
prospective randomized trial comparing
CHOP to CHOP plus rituximab
and to CHOP plus tositumomab/iodine-
131 tositumomab (Bexxar) for
the treatment of newly diagnosed advanced-
stage follicular lymphoma.
Italian Cooperative Study
Group on Lymphoma
The Italian Cooperative Study
Group on Lymphoma has taken a
different tack, comparing FM plus
rituximab to CHOP plus rituximab
as first-line treatment for follicular
lymphoma, according to Dr.
Zinzani, who is at the Institute of
Hematology and Medical Oncology
at the University of Bologna, Italy.
The 12 study centers enrolled 102
patients, 69 of whom were evaluable
for response after completion of chemotherapy.
All patients had histologically
proven CD20-positive follicular
lymphoma and a positive
PCR analysis of bone marrow or
Responders Eligible for
Patients were randomized to six
cycles of fludarabine at 25 mg/m2/d
IV on days 1 to 5 plus mitoxantrone
10 mg/m2 IV on day 1 (n = 36) or to
standard CHOP (n = 33). Those in
PR or CR after chemotherapy and
still PCR positive were eligible for
rituximab at 375 mg/m2 x 4 weeks.
Dr. Zinzani said that CR rates
were 64% after FM and 42% after
CHOP, but that this difference was
not statistically significant (P = .07).
Partial response rates were 31% after
FM vs 28% after CHOP.
Clearance of the bcl-2/IgH chimeric
gene occurred in 34% of patients
after FM and 10% of patients
after CHOP (P = .007). "After
rituximab there was molecular clearance
in 71% of the FM patients and
44% of the CHOP patients, and there
was a measurable improvement of
the clinical response in 50% of PR
patients," said Dr. Zinzani.