Mantle cell lymphoma (MCL) is a recently
identified, aggressive, B-cell neoplasm that is incurable with
current combination chemotherapy regimens. Novel therapeutic
strategies are needed. MCLs express high levels of cell-surface CD20
and are therefore attractive targets for the anti-CD20 monoclonal
antibody, rituximab (Rituxan).
Between May 1997 and March 1999, we enrolled 40 newly diagnosed MCL
patients into a study designed to assess the clinical and molecular
response rate to the combination of rituximab and CHOP
(cyclophosphamide, doxorubicin HCl, Oncovin, and prednisone). Median
patient age was 55 years (range, 31 to 69 years). Stage at
presentation was IV in 33 patients, III in 6 patients, and II in 1
patient. Bone marrow involvement was present at diagnosis in 31
patients. 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.
Grade 4/5 toxicities included one febrile neutropenic death and one
seizure that may have been treatment related. With the exception of
infusional reactions to rituximab, the remaining toxicities were
similar to those expected for CHOP alone.
Response assessment was conducted in a blinded fashion by a
single-study radiologist, using the strict definitions from the
International Workshop to Standardize Response Criteria for
non-Hodgkins lymphoma. Of the 39 patients evaluable for
response, 13 (33%) patients achieved a complete response (CR) and 6
(15%), a complete response, undetermined (CRu); this translated to a
combined CR rate of 48% (two-stage 90% confidence interval [CI], 35%
to 65%). Partial responses (PRs) were achieved in 19 patients, and 1
patient had stable disease. Of the 31 patients with bone marrow
involvement, 21 (68%) patients achieved a pathologic CR in the marrow.
A total of 23 patients had a unique immunoglobulin or bcl-1
rearrangement that could be amplified by polymerase chain reaction
(PCR) and used to assess molecular response. Of the 23 informative
patients, 11 (48%; 90% CI, 30% to 66%) had no evidence of
PCR-detectable disease in the marrow and peripheral blood at the
completion of therapy. Median progression-free survival for study
patients (3 patients were censored at the time of post-study bone
marrow transplantation) is 16.2 months (range, 1.7 to 26.8+ months).
Median follow-up among the 19 patients who have not yet progressed is
CONCLUSION: Taken together, these results suggest that the
combination of rituximab/CHOP is associated with a high rate of
clinical and molecular response in patients with newly diagnosed MCL.
However, many of the responding patients, including those with a
molecular response, have subsequently relapsed. Nevertheless, the
high rate of clinical and molecular CR in the bone marrow and
peripheral blood suggests that rituximab/CHOP induction may provide a
cleaner source of autologous stem cells for additional high-dose and
immunotherapeutic consolidative therapy.