Factors affecting toxicity, response and progression-free survival in relapsed patients with indolent B-cell lymphoma and mantle cell lymphoma treated with rituximab: a Japanese phase II study

• Published in: Annals of oncology Vol. 13; no. 6; pp. 928 - 943
• Main Authors: Igarashi, T., Kobayashi, Y., Ogura, M., Kinoshita, T., Ohtsu, T., Sasaki, Y., Morishima, Y., Murate, T., Kasai, M., Uike, N., Taniwaki, M., Kano, Y., Ohnishi, K., Matsuno, Y., Nakamura, S., Mori, S., Ohashi, Y., Tobinai, K.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-06-2002
• Subjects: Adult; Aged; Analysis of Variance; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Murine-Derived; Antineoplastic agents; Biological and medical sciences; Biopsy, Needle; Confidence Intervals; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Immunotherapy; Japan; Key words: indolent B-cell lymphoma; Lymphoma, B-Cell - drug therapy; Lymphoma, B-Cell - mortality; Lymphoma, B-Cell - pathology; Lymphoma, Mantle-Cell - drug therapy; Lymphoma, Mantle-Cell - mortality; Lymphoma, Mantle-Cell - pathology; Male; mantle cell lymphoma; Maximum Tolerated Dose; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Pharmacology. Drug treatments; Probability; prognostic factor; Risk Factors; Rituximab; serum level; Survival Rate; Treatment Outcome; Asia; Japan; Antineoplastic agent; Human; Relapse; Prognosis; Toxicity; Treatment efficiency; Rituximab; Malignant hemopathy; B-Lymphocyte; Monoclonal antibody; Non Hodgkin lymphoma; Survival; Treatment; Lymphoproliferative syndrome; Low malignancy; Immunotherapy; Mantle cell lymphoma; Predictive factor
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdf155

Background The aim of the study was to determine factors affecting the toxicity and efficacy of rituximab monotherapy in relapsed patients with indolent B-cell lymphoma and mantle cell lymphoma (MCL). Patients and methods A total of 90 patients were enrolled and treated with rituximab infusions at 375 mg/m2 once weekly for 4 weeks. Central pathology review revealed that histologically, 81 patients had indolent B-cell lymphoma or MCL: 59 with follicular lymphoma, 17 with MCL, four with marginal zone lymphoma and one with lymphoplasmacytoid lymphoma. Of these, four were ineligible due to violation of other eligibility criteria. Pre-treatment variables affecting toxicities were analyzed for all 90 patients, and those affecting response and progression-free survival (PFS) were analyzed for 77 eligible patients with confirmed indolent B-cell lymphoma or MCL. The relationship between serum rituximab levels and efficacy was also analyzed for 66 eligible patients. Results Hematological toxicities (grade ≥3) occurred more frequently in females (P <0.05), and thrombocytopenia and leukopenia were more frequent in patients with high lactate dehydrogenase (LDH) levels (P <0.05). Non-hematological toxicities (grade ≥2) were more frequent in patients with extranodal disease or bone marrow involvement. The overall response rate (ORR) in patients receiving one prior chemotherapy regimen was higher than those receiving two or more regimens (P <0.05). The median PFS was shorter in MCL patients, in those with extranodal disease, or in those receiving two or more prior chemotherapy regimens (P <0.01). The PFS intervals of patients with higher serum rituximab levels (≥70 µg/ml) immediately before the third infusion were longer than in other patients (P <0.01). Conclusions Several prognostic factors and serum rituximab levels are useful for predicting the toxicity and efficacy of rituximab monotherapy.