Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma

Purpose: To determine the safety and efficacy of the combination of the chi meric anti-CD20 antibody Rituxan (rituximab, IDEC-C2B8; Genentech Inc, Sout h San Francisco, CA) and cyclophosphamide, doxorubicin, vincristine, and pr ednisone (CHOP) chemotherapy in patients with aggressive non-Hodgkin's lymp homa (NHL), Patients and Methods: Thirty-three patients with previously untreated advan ced aggressive B-cell NHL received six infusions of Rituxan (375 mg/m(2) pe r dose) on day 1 of each cycle in combination with six doses of CHOP chemot herapy given on day 3 of each cycle, Results: The ORR by investigator assessment confirmed by the sponsor was 94 % (31 of 33 patients). Twenty patients experienced a complete response (CR) (61%), 11 patients had a partial response (PR) (33%), and two patients wer e classified as having progressive disease, In the 18 patients with an Inte rnational Prognostic Index (IPI) score greater than or equal to 2, the comb ination of Rituxan plus CHOP achieved an ORR of 89% and CR of 56%, The medi an duration of response and time to progression had not been reached after a median observation rime of 26 months. Twenty-nine of 31 responding patien ts remained in remission during this follow-up period, including 15 of 16 p atients with an IPI score greater than or equal to 2, The most frequent adv erse events attributed to Rituxan were fever and chills, primarily during t he first infusion, Rituxan did not seem to compromise the ability of patien ts to tolerate CHOP; all patients completed the entire six courses of the c ombination. The bcl-2 translocation of blood or bone marrow wets positive a t baseline in 13 patients; 11 patients had follow-up specimens obtained (ei ght CR, three PR), and all had a negative bcl-2 status after therapy. Only one patient has reconverted to bcl-2 positivity, and all patients remain in clinical remission. Conclusion: This is the first report to demonstrate the safety and efficacy of the Rituxan chimeric anti-CD20 antibody in combination with standard-do se CHOP in the treatment of aggressive B-cell lymphoma. The clinical respon ses are at least comparable to those achieved with CHOP alone with no signi ficant added toxicity. The presence or absence of the bcl-2 translocation d id not affect the ability of patients to achieve a CR with this regimen. Th e ability to achieve sustained remissions in patients with an IPI score gre ater than or equal to 2 warrants further investigation with a randomized st udy. J Clin Oncol 19:389-397. (C) 2001 by American Society of Clinical Onco logy.