MIAMI BEACHLong-term follow-up of the pivotal trial of
rituximab (Rituxan) in patients with relapsed or refractory low-grade
or follicular B-cell non-Hodgkins lymphoma (NHL), shows a
median duration of response of nearly 1 year (11.6 months), Peter
McLaughlin, MD, reported at a poster session of the American Society
of Hematology (ASH) meeting.
As previously reported, 80 of 166 patients (48%) responded to
rituximab, an anti-CD20 chimeric monoclonal antibody, with 6%
complete responses. To date, 20 of the 80 responders (25%) are still
in remission, some up to 3 years after treatment, said Dr.
McLaughlin, associate professor of medicine, M.D. Anderson Cancer Center.
This study also confirmed that patients treated with rituximab
after their first chemotherapy relapse had a higher response rate
(57%) than those treated after second (46%) or third relapses from
chemotherapy (38%), Dr. McLaughlin said. In refractory
patients, the overall response rate was 29% (6 of 21).
Co-author Antonio Grillo-López, MD, chief medical officer of
IDEC Pharmaceuticals, said at a press briefing that since treatment
of these patients is rarely curative, the therapeutic goal is not
necessarily complete response rate but rather overall response rate
and longer duration of responses.
Also at ASH, Thomas Davis, MD, of the National Cancer Institute,
presented data showing that patients who respond to rituximab can be
safely retreated in case of relapse. This phase II study enrolled 58
patients with relapsed or chemotherapy refractory low-grade or
follicular B-cell non-Hodgkins lymphoma who had responded to rituximab.
40% Responded a Second Time
Of 57 patients evaluable for efficacy, 23 (40%) responded a second
time to rituximab, with 6 (11%) complete re-sponses. To date, the
median duration of response is 15+ months (range, 2.5 to 25.1
months), and median time to progression is 16.7+ months (range, 4.6
to 26.6 months).
Dr. Grillo-López said that Rituxan can be used to
retreat patients without impairing bone marrow function and at the
same time deferring toxic alternative treatments. Adverse events seen
with retreatment were similar to those seen with initial treatment.
Of interest, five patients have received a third course of rituximab:
Three of these responded, one had stable disease, and one was not
evaluable for efficacy. One patient has subsequently received a
fourth course of rituximab treatment.
Dr. Grillo-López presented a report on the response criteria
used in the rituximab pivotal trial. Presently, he said,
there are no standard response criteria for non-Hodgkins
lymphoma as there are for solid tumors, chronic lymphocytic leukemia,
and Hodgkins disease. Without standard criteria, physicians
have no benchmark for evaluating reported response rates of various
He noted that a group of non-Hodgkins lymphoma experts
established the stringent response criteria that were applied in the
rituximab studies. Subsequently, he said, a panel
of international lymphoma experts, along with the National Cancer
Institute, have utilized our response criteria as the basis for
development of standardized response criteria for measuring tumor
sizes and classifying responses in patients with non-Hodgkins lymphoma.
To show how the response criteria used can affect results, the
researchers applied three different response criteria to the
rituximab database. Using the most stringent criteria for normal
lymph node size of 1 cm × 1 cm , the complete response rate for
rituximab was 6% (as reported in the pivotal trial). When measured by
the less stringent criteria of 1.5 × 1.5 cm, or 2 × 2 cm,
the complete response rates climbed to 18% and 28%, respectively.
Thus, without clearly defined or standard response criteria for
non-Hodgkins lymphoma, reports in the literature of anticancer
agent results must be weighed carefully, he said. A
standardized approach will allow physicians to accurately assess new
biological agents for non-Hodgkins lymphoma.
Where Does Rituximab Fit?
David Maloney, MD, PhD, of Fred Hutchinson Cancer Research Center,
said at the press briefing that antibody-based treatments offer
exciting new possibilities for the treatment of patients with
lymphoma. However, their exact role remains to be defined.
He noted that with rituximab, there has been no identified
cumulative toxicity, the treatment is relatively easy and can be done
in the outpatient setting, and responses have been seen in patients
with very large tumors, extensive bone marrow involvement, and
Radiolabeled antibodies currently under investigation will also
add to the treatment choices of patients with lymphoma, Dr.
Maloney said. However, he added that these treatments are
generally more complicated, have dose-limiting toxicities, and are
more difficult to combine with our current chemotherapy regimens.
Dr. Maloney said that in managing patients with low-grade lymphomas,
I try to consider not only the current clinical situation of
the patient but also the subsequent treatment that the patient will
For example, he said, damage to the bone marrow or the development of
an immune response or HAMA (human anti-murine antibody) may limit
future treatment options with other chemotherapy regimens or other
This appears more likely with current radiolabeled murine
antibodies, and I generally reserve their use for patients who have
failed treatment with rituximab. However, this issue is very
complicated, and we dont yet have any clinical trial data to
determine optimal sequencing.
IDEC Pharmaceuticals developed rituximab in collaboration with
Genentech, Inc., F. Hoffmann-La Roche, Ltd of Switzerland, and
Zenyaku Kogyo Co, Ltd. of Japan. The agent was approved for marketing
by the Food and Drug Administration in November 1997, and since then
has been used to treat more than 12,000 lymphoma patients worldwide.