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Monoclonal antibodies for the treatment of hematologic malignancies: clinical trials in Japan

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Abstract

Of 12 patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma (B-NHL) enrolled in a phase I study of rituximab, 11 were eligible, and of these 2 achieved a complete response and 5 a partial response. The elimination half-life of rituximab was 445±361 h, and serum rituximab levels were detectable at 3 months. In a phase II study, 90 patients with relapsed indolent B-NHL or mantle cell lymphoma (MCL) were treated with infusions of rituximab 375 mg/m2 once weekly for four doses. The overall response rate in indolent B-NHL and MCL was 61% (37/61, 95% CI 47–73%) and 46% (6/13, 95% CI 19–75%), respectively. The median progression-free survival (PFS) was shorter in MCL patients, in those with extranodal disease, and in those who had received two or more prior chemotherapy regimens (P<0.01). Rituximab retreatment was well tolerated in 13 patients with relapsed indolent B-NHL and there were no grade 3/4 nonhematologic toxicities. Partial response was observed in five (38%, 95% CI 14–68%) patients, and the median PFS after retreatment was 5.1 months. In a single-agent phase II study of infusions of rituximab 375 mg/m2 once weekly for eight doses against relapsed aggressive B-NHL showed, 21 (37%, 95% CI 24–51%) of the 57 eligible patients responded. In conclusion, rituximab is a highly effective agent in relapsed indolent and aggressive B-NHL and MCL with acceptable toxicities. Yttrium-90 provides advantages over iodine-131 because it delivers higher β energy. In 2002, we initiated a feasibility study of yttrium-90-labeled ibritumomab tiuxetan for relapsed indolent B-NHL in Japan. Gemtuzumab ozogamicin (CMA-676) is a calicheamicin-conjugated humanized anti-CD33 monoclonal antibody. Of 20 patients with relapsed or refractory acute myeloid leukemia enrolled in a "bridging" phase I/II study, 7 showed an objective response. It is concluded that monoclonal antibodies will have play a significant role in the treatment of hematologic malignancies in the future.

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Acknowledgements

Clinical studies of rituximab were supported in part by Zenyaku Kogyo Company Ltd., Tokyo, Japan. We thank all the investigators, including the physicians and nurses in the institutions participating in Japanese multicenter trials. We thank the members of the Central Pathology Review Committee, the Independent Computed Tomography Review Committee, and the Independent Data Monitoring Committee.

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  1. Hematology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, 104-0045, Tokyo, Japan

    Kensei Tobinai

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  1. Kensei Tobinai
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Correspondence to Kensei Tobinai.

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Tobinai, K. Monoclonal antibodies for the treatment of hematologic malignancies: clinical trials in Japan. Cancer Chemother Pharmacol 52 (Suppl 1), 90–96 (2003). https://doi.org/10.1007/s00280-003-0595-y

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