Originally published as JCO Early Release 10.1200/JCO.2005.17.129 on August 29 2005

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Clinical Outcomes in t(4;14) Multiple Myeloma: A Chemotherapy-Sensitive Disease Characterized by Rapid Relapse and Alkylating Agent Resistance

From the Department of Medical Oncology and Hematology; Department of Laboratory Medicine and Pathobiology, Princess Margaret Hospital/University Health Network; and McLaughlin Centre for Molecular Medicine, University of Toronto, Toronto, Canada

Address reprint requests to A. Keith Stewart, MD, McLaughlin Centre for Molecular Medicine, 620 University Avenue, Suite 8-202, Toronto, Ontario, Canada M5G 2C1; e-mail: kstewart{at}uhnres.utoronto.ca

PURPOSE: To determine whether primary drug resistance or rapid relapse explains the poor prognosis seen in t(4;14)-positive multiple myeloma (MM).

PATIENTS AND METHODS: A total of 131 patients treated with high-dose therapy (HDT) were assessed, of whom 19 were t(4;14) positive. We examined the presentation features, chemotherapy responsiveness at presentation and to salvage therapies at relapse, and overall survival outcomes.

RESULTS: t(4;14)-positive patients had a predominance of the immunoglobulin A isotype (52.6%) but otherwise baseline characteristics were indistinguishable. After treatment with vincristine, doxorubicin, and dexamethasone or dexamethasone alone, 17 (89.7%) of the 19 patients achieved a partial response and 11 patients (57.9%) demonstrated an additional 50% reduction in paraprotein after HDT. Thus, t(4;14)-positive patients are chemotherapy sensitive; however, early progression was common, with 26% of patients progressing before HDT and a median progression-free survival after HDT of only 14.1 months. At relapse, a resistance to alkylating agents was evident, with no responses (zero of 11 patients) seen with conventional-dose alkylating agents. Salvage regimens using thalidomide and/or dexamethasone achieved at least minimal response in 59% of patients. The duration of response was short, however, with a median of only 4.7 months. The median overall survival after HDT was 24.2 months.

CONCLUSION: We conclude that t(4;14)-positive MM is chemotherapy sensitive but rapid relapse occurs. Resistance to alkylating agents is evident at relapse. The development of novel therapeutic agents is required, including the early clinical study of targeted fibroblast growth factor receptor 3 tyrosine kinase inhibitors, which have shown promise in preclinical studies.

Supported by grants from the Multiple Myeloma Research Foundation, the National Cancer Institute of Canada, and the Canadian Institutes for Health Research.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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