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Originally published as JCO Early Release 10.1200/JCO.2008.19.2468 on October 6 2008 © 2008 American Society of Clinical Oncology.
In Reply
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan Ferreri et al corresponded to our recent report1 and revealed important findings concerning the role of rituximab in the treatment of intravascular large B-cell lymphoma (IVLBCL). They conducted a multilateral retrospective analysis of IVLBCL in Western countries, and found that response rate to treatment and survival duration for IVLBCL in the rituximab era were superior to those in the prerituximab era in Western countries. Given our recent study, the results of retrospective analyses from two different areas (Western and Asian) are coincident, and these two reports strongly suggest that the natural history of IVLBCL could be changed by rituximab-containing chemotherapies, and addition of rituximab to chemotherapies might be effective for both Western and Asian types of IVLBCL. In our recent report,1 median follow-up duration for survivors was 18 months, whereas median follow-up duration in the correspondence from Ferreri et al was 2 years, slightly longer than ours. We have recently presented updated follow-up data for our cohort at the 10th International Conference on Malignant Lymphoma. With a median follow-up duration of 26 months for patients in the rituximab-containing chemotherapy group, overall and progression-free survival rates at 3 years were 60% and 53%, respectively. This result indicates that the clinical outcomes for rituximab-containing chemotherapies remain in keeping for greater than 2 years of follow-up. In the correspondence, adverse drug reaction as a result of rituximab treatment was observed in six (18%) of 34 patients, whereas 29% of patients experienced adverse drug reaction in our cohort. This difference might be attributable to differences in the clinical presentation of IVLBCL between Asian and Western countries. If we consider the severe infusion reactions previously reported, optimal timing of the first dose of rituximab is important in the treatment of IVLBCL. In our analysis,1 grade 3 hypoxia was observed in one patient who received rituximab on the first day of treatment. We thus agree that delaying rituximab administration by several days in the first course of the treatment might offer a useful way to avoid severe infusion reactions to rituximab, as Ferreri et al suggested, particularly in patients with severe organ damage. CNS involvement remains a serious issue in IVLBCL. In our analysis,1 about one fourth of patients who achieved complete response developed CNS relapse during the clinical course. No difference in CNS relapse rate was seen between patients treated with chemotherapies with or without rituximab (Shimada, manuscript in preparation). These results strongly suggest that CNS relapse in IVLBCL could not be overcome by the introduction of rituximab. The role of CNS-oriented therapies in the treatment for IVLBCL should thus be investigated in the future. Our report1 and the correspondence from Ferreri et al highlight several issues that remain yet to be solved. Two retrospective studies have shown that addition of rituximab to chemotherapies improved clinical outcomes in both Asian and Western countries, and these results should be validated in prospective trials. Second, optimal combination regimens are still to be determined. Since CNS relapse has not been resolved, as mentioned above, CNS-oriented drugs such as a high-dose methotrexate and intrathecal chemotherapies need to be included in the first-line treatment. Future prospective studies are required regarding these residual issues to establish optimal treatment strategies for IVLBCL. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: None Stock Ownership: None Honoraria: Kazuyuki Shimada, Chugai Pharmaceutical Co Ltd; Tomohiro Kinoshita, Chugai Pharmaceutical Co Ltd Research Funding: None Expert Testimony: None Other Remuneration: None NOTES published online ahead of print at www.jco.org on October 6, 2008 REFERENCE
1. Shimada K, Matsue K, Yamamoto K, et al: Retrospective analysis of intravascular large B-cell lymphoma treated with rituximab-containing chemotherapy as reported by the IVL study group in Japan. J Clin Oncol 26:3189-3195, 2008
Related Correspondence
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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