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
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-Hodgkin’s 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 11.7 months.
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.