Rituximab/CHOP Yields High Initial Response in Mantle Cell Lymphoma

BOSTON-Adding 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.”