SAN DIEGO--New data on rituximab (Rituxan), a chimeric anti-CD20
monoclonal antibody, show a projected median time to progression of
13 months among patients who responded to the drug (76 of 166
patients with relapsed or refractory indolent lymphoma). To date,
nearly 70% of these patients (53) continue to respond to outpatient
therapy with rituximab; only nine have died, all of progressive lymphoma.
Last year, rituximab became the first monoclonal antibody approved
for the treatment of cancer when it received the FDAs nod for
use as a single agent in patients with relapsed or refractory low-grade
or follicular, CD20-positive B-cell non-Hodgkins lymphoma. The
agent is given in four infusions over a 22-day period in an
The current report of the pivotal trial, conducted at 31 US sites,
provides data on the 166 intent-to-treat patients, with a median
follow-up of 11.8 months (J Clin Oncol 16:2825-2833, 1998).
The results show a 48% overall response rate for rituximab as a
single agent. "Most of the responses were partial (42%), which
is typical of single-agent therapy in the setting of relapsed
lymphoma," said Peter McLaughlin, MD, associate professor of
medicine, M.D. Anderson Cancer Center, and lead author of the study.
"These results are comparable to some of the most encouraging
recent chemotherapy results for relapsed indolent lymphomas, such as
with fludarabine [Fludara] or 2-chlorodeoxy-adenosine [cladribine, Leustatin]."
Among the responders to rituximab, the median duration of response to
prior chemotherapy was 12 months, about equal to that seen with
rituximab (13 months), although in the natural course of the disease,
each subsequent remission usually is of shorter duration.
Toxicity Notably Mild
The researchers reported that toxicity "was notably mild,
particularly with respect to myelosuppressive toxicities that are
typical of standard chemotherapy or RIT [radioimmunotherapy]."
The majority of adverse events occurred during the first infusion and
were grade 1 or 2, with fever and chills the most common.
Only 12% of patients had grade 3 toxicities, and only 3% had grade 4
events. Human antichimeric antibody (HACA) was detected in only one
patient and was not associated with any clinical or laboratory
abnormalities. "By virtue of the modest toxicities of this
agent, which do not overlap with the toxicities of standard
chemotherapy, this agent lends itself to integration with
chemotherapy programs," the investigators said.
Median serum antibody levels were higher for responders than for
nonre-sponders. The researchers speculate that higher doses or more
protracted dosing schedules might lead to higher antibody levels and,
conceivably, higher response rates.
"These good response rates and time to progression data, along
with the mild toxicity profile, suggest that rituximab as a single
agent is an appropriate new treatment option for patients with
relapsed indolent lymphoma," Dr. McLaughlin said. "It is
also a very appealing agent to consider for further investigation,
such as in an adjuvant role or in conjunction with chemotherapy."