Monoclonal Antibody Adds Punch to CHOP

NEW YORK—Rituximab (Rituxan) used in combination with standard chemotherapy may prolong the duration of response for patients with B-cell non-Hodgkin’s lymphoma (NHL), Myron S. Czuczman, MD, said at the Chemotherapy Foundation Symposium VII.

Dr. Czuczman, head of the Lymphoma Service at Roswell Park Cancer Institute, reported on a phase II study of rituximab, a chimeric anti-CD20 monoclonal antibody, used with standard CHOP chemotherapy.

Initially responsive to systemic chemotherapy, NHL nonetheless relapses in the majority of cases, and the duration of response is shorter with each subsequent relapse. The median survival for NHL is 6.2 years, but it falls to less than 5 years after the first relapse. “New treatments are needed because existing ones have no impact on survival of relapsed NHL,” Dr. Czuczman said.

The rationale for combining rituximab with CHOP is its demonstrated efficacy as a single agent, the absence of cross-resistance and overlapping toxicity with any of the CHOP components, and in vitro data suggesting its ability to sensitize chemoresistant cell lines.

The multicenter trial enrolled 40 patients with low-grade or follicular lymphoma, 31 newly diagnosed and 9 relapsed after prior treatment.

The patients received six cycles of standard-dose CHOP (cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², and vincristine 1.4 mg/m² intravenously on day 1; and 100 mg/m² oral prednisone on days 1 through 5) every 3 weeks Rituximab was given as a 375 mg/m² infusion as follows: 7 and 2 days before the first CHOP cycle, 2 days before the third and fifth CHOP cycle, and two times 7 days apart following the final CHOP cycle. “The first two doses served as induction; the ones before the third and fifth cycles were intended to utilize the synergy with the CHOP agents; and the last two aimed to mop up any residual disease,” Dr. Czuczman explained.

Adverse events were minimal and consisted primarily of grade 1 and 2 flulike symptoms, he said, adding that the overall toxicity was similar to that seen with CHOP alone. Grade 3 and 4 events, including hematologic and infectious toxicities, were attributed to CHOP.

The 35 patients who completed treatment had a response rate of 95%, with 55% (22 patients) achieving a complete response and 40% (16 patients), a partial response. Median duration of response was 39.1+ months. Median time to progression had not been reached after 40.5+ months. Dr. Czuczman said the response rate was at least equivalent to that seen in CHOP alone. Evidence suggesting that rituximab was also able to clear minimal residual disease, which has not been demonstrated with CHOP alone, supports its use in this setting, he said.