BOSTONAdding rituximab (Rituxan) to cyclophosphamide,
doxorubicin, vincristine, prednisone (CHOP) induction therapy may
provide a cleaner source of autologous stem cells for use following
high-dose therapy in mantle cell lymphoma, Orion Howard, MD, reported
at the ASH meeting.
The combination of rituximab/CHOP is associated with a high
rate of clinical, bone marrow, and molecular response in patients
with newly diagnosed mantle cell lymphoma, Dr. Howard stated.
Although many of the responding patients subsequently relapsed,
including those with molecular complete responses, peripheral blood
stem cells collected during the period of complete remission may have
potential for use in later consolidative therapy following high-dose chemotherapy.
Can Therapy Induce Responses?
Dr. Howard and colleagues at the Dana-Farber Cancer Institute and at
Massachusetts General Hospital enrolled 40 patients newly-diagnosed
with mantle cell lymphoma into a study designed to assess the ability
of the rituximab/CHOP combination to induce clinical and molecular
responses. Median patient age was 55 years (range 31 to 69 years). At
study entry, 33 patients had stage IV disease; 6 had stage III; and 1
had stage II.
Treatment consisted of six cycles of therapy at 21-day
intervals, with rituximab on day 1 (375 mg/m²) and standard CHOP
on day 3, Dr. Howard said.
49% Complete Response
At the time of the presentation at the ASH meeting, the complete
response (CR) rate among the 39 of 40 evaluable patients was 49% (see Table
1). Dr. Howard said that there was pathologic CR in 21 of the 31
patients (68%) with bone marrow involvement.
There were 23 patients with unique immunoglobulin or bcl-1 gene
rearrangements that could be amplified by polymerase chain reaction
(PCR) and used to assess molecular response. Of these 23 patients, 11
(48%) had no molecular evidence of disease in the bone marrow or
peripheral blood following rituximab/CHOP treatment. Median
progression-free survival was 16.2 months.
Many Responders Relapsed
Many of the responding patients eventually relapsed, including some
patients who had molecular complete responses. Twenty patients
have progressed, and 19 have not progressed, Dr. Howard said.
We were surprised to find that molecular responses did not
correlate with duration of response. One patient died during
therapy. The remaining 20 patients are alive and in best response
4.2+ to 26.8+ months after starting therapy.
Dr. Howard said that the one death was associated with febrile
neutropenia. In addition, there was one seizure that may have been
treatment related. With the exception of infusional reactions to the
rituximab, the remainder of the toxicities were similar to those
expected for CHOP alone.
I think that rituximab/CHOP may have a role as a better
induction regimen for other consolidative therapy such as autologous
bone marrow transplant or additional therapy, Dr. Howard said
in an interview. Mantle cell lymphoma continues to be a disease
with a high propensity for relapse, and it is likely to require a
multifaceted approach to achieve long-term success.