HOUSTONLong-term follow-up of the rituximab (Rituxan)
pivotal trial in relapsed or refractory non-Hodgkins lymphoma
(NHL) shows a median response duration of almost a year. The
anti-CD20 chimeric monoclonal antibody was approved last year for use
in relapsed or refractory low-grade or follicular NHL.
In a poster presentation at the American Society of Hematology
meeting, Peter McLaughlin, MD, of M.D. Anderson Cancer Center,
reported the long-term follow-up results as well as a comparison of
response data with internal and external controls.
Patients were treated with rituximab at 375 mg/m² weekly for 4
weeks. Using intention-to-treat analysis, the overall response rate
in the 166 study patients was 48% (CR 6%, PR 42%). Median duration of
response was 11.6 months, and median time to progression was 13.2
months. Of 80 responders, 20 (25%) have an ongoing reponse, with a
duration range of 19.3+ months to 36.7 months.
The overall response rate did not vary significantly with the number
of prior chemotherapy courses but decreased, as expected, with the
number of relapses: 57% for one relapse, 46% for two relapses, and
38% for three.
Refractory patients with zero relapses (never responded, never
relapsed) had an overall response rate of 29% (6 of 21). Responses
were confirmed on CT scans in a blinded audit by independent lymphoma
experts using rigorous response criteria .
The researchers analyzed 22 of the most important factors for NHL
prognosis, including age, bulky disease, IWF histologic type, prior
autologous bone marrow transplant (ABMT), bcl-2 positivity, bone
marrow involvement, extranodal disease, number of relapses, and
resistance to the last chemotherapy course. Only three factors
emerged as significant: histologic type, bcl-2 status at baseline,
and prior ABMT.
Historical Controls Used
Although comparison with randomized controls would have been ideal,
there were problems with this approach. Selection of an appropriate
control group in these NHL patients is difficult, Dr. McLaughlin
(1) there is no standard treatment; (2) patients may find
randomization into the chemotherapy arm less desirable than the
immunotherapy arm (due to toxicity and longer time required for
treatment); and (3) randomized studies evaluating treatments with
similar response rates require large numbers of patients, are costly,
and take several years to complete.
Instead, the researchers used two types of historical controls:
internal, in which the patients served as their own controls, and
extermal, using comparisons to reports in the literature.
Intention-to-treat analysis of responses with patients serving as
their own controls found no significant difference in duration of
response compared to responses with prior therapy. As
expected, Dr. McLaughlin said, overall response rates
decreased with increasing number of relapses. Nevertheless, patients
with three relapses had a 38% overall response rate, and refractory
patients had a 29% overall response rate.
Using historical data from the literature, rituximab compared
favorably to other single-agent therapies such as cladribine
(Leustatin) and fludarabine (Fludara) (see Table).
A short (four infusions, 22 days) outpatient course of
rituximab produces responses in patients with relapsed/refractory low-grade
or follicular NHL of equivalent duration to prior chemotherapy. The
overall response rate obtained with rituximab compares favorably to
that of other single agents, he concluded.
Initial studies in combination with chemotherapeutic and biologic
agents have shown promising results, he added, and rituximab is now
being evaluated in large randomized studies in patients with