Phase II Study of Rituximab in Combination With CHOP in Patients With Previously Untreated Intermediate- or High-Grade Non-Hodgkin’s Lymphoma

The rationale for combining rituximab (Rituxan), a chimeric anti-CD20 monoclonal antibody, with chemotherapy includes single-agent efficacy, non–cross-resistant mechanisms of action, possible synergy, and few overlapping toxicities. The safety and efficacy of rituximab plus CHOP (cyclophosphamide, doxorubicin, Oncovin [vincristine], and prednisone) were evaluated in a previous phase II study in patients with low-grade/follicular non-Hodgkin’s lymphoma (NHL). The overall response rate in 35 evaluable patients was 100% (63% complete responses [CRs], 37% partial responses [PRs]). Median duration of response was 39.1+ months.

A total of 33 patients with untreated intermediate- or high-grade NHL were enrolled in the present study evaluating the clinical effects of the combination of rituximab administered on day 1 of each 21-day cycle followed by CHOP (cyclophosphamide, 750 mg/m² on day 3; doxorubicin, 50 mg/m² on day 3; vincristine, 1.4 mg/m² on day 3; and prednisone, 100 mg on days 3 to 7). The median age of patients was 52 years (range, 20 to 79 years). Of the 33 patients, 24 had stage III/IV disease; 8, stage II disease; and 1, bulky stage IE disease. Ten patients had one single mass ³ 10 cm, and 18 had extranodal disease. A total of 17 patients were classified as International Prognostic Index (IPI) ³ 2, and two-thirds had diffuse large-cell disease. All 33 patients completed six cycles of CHOP and were evaluable for response.

The overall response rate was 97% (32/33), with 20 CRs, 12 PRs, and 1 case of progressive disease (PD). With a median follow-up of 24 months, the median response duration was 18+ months (range, 12 to 32+ months). Among evaluable patients, 27 (including 7 with PRs) showed no evidence of progressive disease, and 4 partially responding patients received additional therapy. (One partial responder progressed and is in remission after subsequent chemotherapy/surgery, and three are in continued remission with local radiation therapy only.) A total of 13 patients were bcl-2–positive in bone marrow or peripheral blood at study initiation, 11 patients had subsequent negative samples, and 10 remain negative.

Serious adverse events were similar to those associated with conventional CHOP alone. Hematologic toxicity included grade 4 neutropenia in 18 patients and grade 3 neutropenia in 12 patients. One or more courses of granulocyte colony-stimulating factor

(Neupogen) were required in 18 patients, and hospitalization was needed in 14 patients. Neutropenic fever and dehydration were the most common causes. One patient was hospitalized during cycle 1 for hypotension and bradycardia related to infusion of rituximab but completed the infusion and the study. Two deaths occurred during the study. One death was due to progressive disease (52 weeks) and the other, to stroke (28 weeks).

CONCLUSION: Rituximab plus CHOP is safe in patients with intermediate- or high-grade NHL, and initial data indicate that this regimen has an excellent overall response rate. To evaluate the potential for cure with the combination of rituximab plus CHOP, a large randomized trial is planned.

Click here for Dr. Bruce Cheson’s commentary on this abstract.