Clinical outcomes in t(4;14) multiple myeloma

A chemotherapy-sensitive disease characterized by rapid relapse and alkylating agent resistance

Wilfrid Jaksic, Suzanne Trudel, Hong Chang, Young Trieu, Xi Qi, Joseph R Mikhael, Donna Reece, Christine Chen, Alexander Keith Stewart

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7069-7073
Number of pages5
JournalJournal of Clinical Oncology
Volume23
Issue number28
DOIs
StatePublished - 2005
Externally publishedYes

Fingerprint

Alkylating Agents
Multiple Myeloma
Recurrence
Drug Therapy
Dexamethasone
Therapeutics
Receptor, Fibroblast Growth Factor, Type 3
Paraproteins
Salvage Therapy
Thalidomide
Survival
Immunoglobulin Isotypes
Vincristine
Drug Resistance
Protein-Tyrosine Kinases
Doxorubicin
Immunoglobulin A
Disease-Free Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Clinical outcomes in t(4;14) multiple myeloma : A chemotherapy-sensitive disease characterized by rapid relapse and alkylating agent resistance. / Jaksic, Wilfrid; Trudel, Suzanne; Chang, Hong; Trieu, Young; Qi, Xi; Mikhael, Joseph R; Reece, Donna; Chen, Christine; Stewart, Alexander Keith.

In: Journal of Clinical Oncology, Vol. 23, No. 28, 2005, p. 7069-7073.

Research output: Contribution to journalArticle

Jaksic, Wilfrid ; Trudel, Suzanne ; Chang, Hong ; Trieu, Young ; Qi, Xi ; Mikhael, Joseph R ; Reece, Donna ; Chen, Christine ; Stewart, Alexander Keith. / Clinical outcomes in t(4;14) multiple myeloma : A chemotherapy-sensitive disease characterized by rapid relapse and alkylating agent resistance. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 28. pp. 7069-7073.
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abstract = "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.",
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T1 - Clinical outcomes in t(4;14) multiple myeloma

T2 - A chemotherapy-sensitive disease characterized by rapid relapse and alkylating agent resistance

AU - Jaksic, Wilfrid

AU - Trudel, Suzanne

AU - Chang, Hong

AU - Trieu, Young

AU - Qi, Xi

AU - Mikhael, Joseph R

AU - Reece, Donna

AU - Chen, Christine

AU - Stewart, Alexander Keith

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

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DO - 10.1200/JCO.2005.17.129

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