Monoclonal Antibody Therapy for B-Cell Lymphoma: Clinical Trials of an Anti-CD20 Monoclonal Antibody for B-Cell Lymphoma in Japan

Abstract

Twelve patients with relapsed CD20+ B-cell non-Hodgkin’s lymphoma (B-NHL) were enrolled in a phase I study of rituximab; 4 received rituximab 250 mg/m2 and 8 received rituximab 375 mg/m2 once weekly for 4 weeks. Grade 1 or 2 infusion-related toxicity was observed. Of the 11 eligible patients, 2 achieved complete responses and 5 achieved partial responses. The elimination half-life (T1/2) of rituximab was 445 ± 361 hours, and serum rituximab levels were detectable at 3 months. There after, 90 relapse patients with indolent B-NHL or mantle cell lymphoma (MCL) were enrolled in a phase II study and treated with rituximab at 375 mg/m2 per infusion in 4 weekly infusions. Sixteen patients were ineligible in protocol compatible analyses. The overall response rates (ORR) in indolent B-NHL and MCL were 61% (37 of 61 patients) and 46% (6 of 13 patients), respectively. Factors affecting response and progression-free survival (PFS) were analyzed for 77 patients whose histopathology was centrally confirmed as indolent B-NHL or MCL. The ORR in patients receiving 1 prior chemotherapy regimen was higher than the ORR in those receiving ≥ 2 regimens (P < .05). The median PFS was shorter in MCL patients, in those with extranodal disease, and in those receiving ≥2 prior chemotherapy regimens (P < .01). The PFS of patients with higher serum rituximab levels (≥70 μxg/mL) immediately before the third infusion was longer than that of other patients (P < .01). Several pretreatment factors and serum rituximab levels are useful for predicting the efficacy of rituximab monotherapy. Rituximab re-treatment was well tolerated in 13 patients with no grade 3 or 4 nonhematological toxicities. A partial response was observed in 5 patients (38%), and the median PFS after re-treatment was 5.1 months. In conclusion, rituximab is a highly effective agent in relapsed indolent and aggressive B-NHL and MCL and has acceptable toxicities.Int J Hematol. 2002;76:411-419.

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Correspondence to Kensei Tobinai.

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Tobinai, K. Monoclonal Antibody Therapy for B-Cell Lymphoma: Clinical Trials of an Anti-CD20 Monoclonal Antibody for B-Cell Lymphoma in Japan. Int J Hematol 76, 411–419 (2002). https://doi.org/10.1007/BF02982806

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Key words

  • Monoclonal antibody therapy
  • CD20
  • B-cell lymphoma
  • Rituximab
  • Chimeric antibody