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다발성 골수종 환자에서 Bortezomib에 의한 말초신경병증 발생과 위험인자 분석

Analysis of Incidence and Risk Factors for Bortezomib-induced Peripheral Neuropathy in Multiple Myeloma

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Bortezomib acts by disrupting ubiquitin-proteasome pathway which regulates proteinhomeostasis within the cell and has demonstrated significant activity mainly against recurrent ornewly diagnosed multiple myeloma(MM). Among bortezomib-related side effects, peripheral neuropathy(PN) as main dose-limiting non-haematological toxicity can substantially affect thequality of life of patients. It typically requires dose-reduction, delay, or even premature terminationof successful treatment. Therefore, predicting the risk for neuropathy before the therapyand a proper management of neurotoxicity are very important considerations. The aim of this study was to evaluate the incidence of PN, risk factors, and prior exposure topotentially neurotoxic chemotherapy. A total of 108 patients with multiple myeloma(MM) wereincluded, who received bortezomib in Seoul National University of Hospital(SNUH) from May 2005 to April 2008. A retrospective chart review was performed on SNUH patients’ElectronicMedical Records(EMR), and the SPSS Statistics 19.0 was used for analysis. In univariate analysis, no correlation was found between the development of PN, sex, or age,but creatinine level (Scr≥2)(48% vs 78%, p=0.007, OR=0.264), presence of DM(50% vs 76%,p=0.034, OR=0.324) and number of therapy cycles(N>3)(84% vs 57%, p=0.002, OR=4.046) weresignificantly correlated with PN incidence. In a multivariate logistic regression, the risk of bortezomib-related PN was lower in patients whose creatinine level was high(Scr≥2)(OR=0.248) andgreater in patients treated with high number of bortezomib cylces(N>3)(OR=4.235). Concerning that the prior exposure to chemotherapy could exacerbate neurotoxicity, there waslower incidence of PN in the prior bortezomib treated group(38% vs 62%, p=0.007), prior bortezomibwith thalidomide treated group(36% vs 63%, p=0.003), and prior bortezomib with vincristinetreated group(37% vs 60%, p=0.026).

Bortezomib acts by disrupting ubiquitin-proteasome pathway which regulates proteinhomeostasis within the cell and has demonstrated significant activity mainly against recurrent ornewly diagnosed multiple myeloma(MM). Among bortezomib-related side effects, peripheral neuropathy(PN) as main dose-limiting non-haematological toxicity can substantially affect thequality of life of patients. It typically requires dose-reduction, delay, or even premature terminationof successful treatment. Therefore, predicting the risk for neuropathy before the therapyand a proper management of neurotoxicity are very important considerations. The aim of this study was to evaluate the incidence of PN, risk factors, and prior exposure topotentially neurotoxic chemotherapy. A total of 108 patients with multiple myeloma(MM) wereincluded, who received bortezomib in Seoul National University of Hospital(SNUH) from May 2005 to April 2008. A retrospective chart review was performed on SNUH patients’ElectronicMedical Records(EMR), and the SPSS Statistics 19.0 was used for analysis. In univariate analysis, no correlation was found between the development of PN, sex, or age,but creatinine level (Scr≥2)(48% vs 78%, p=0.007, OR=0.264), presence of DM(50% vs 76%,p=0.034, OR=0.324) and number of therapy cycles(N>3)(84% vs 57%, p=0.002, OR=4.046) weresignificantly correlated with PN incidence. In a multivariate logistic regression, the risk of bortezomib-related PN was lower in patients whose creatinine level was high(Scr≥2)(OR=0.248) andgreater in patients treated with high number of bortezomib cylces(N>3)(OR=4.235). Concerning that the prior exposure to chemotherapy could exacerbate neurotoxicity, there waslower incidence of PN in the prior bortezomib treated group(38% vs 62%, p=0.007), prior bortezomibwith thalidomide treated group(36% vs 63%, p=0.003), and prior bortezomib with vincristinetreated group(37% vs 60%, p=0.026).

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