Background Although previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma （RRMM）, the optimal dose combinations of bortezom...Background Although previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma （RRMM）, the optimal dose combinations of bortezomib and dexamethasone remain unknown. This trial aimed to observe the efficacy and safety of different dose combinations of bortezomib and dexamethasone in the treatment of RRMM patients in China.Methods A total of 168 patients with relapsed multiple myeloma （MM） who were refractory to at lest two prior treatments were enrolled in this multicenter, open-label, non-randomized, prospective clinical trial. Twenty patients received 1.3 mg/m2 of bortezomib twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles and oral or intravenous dexamethasone 20 mg on the day of and after each bortezomib dose （group 1）; 66 patients received less than 1.3 mg/m2（0.7-1.0 mg/m2） of bortezomib and dexamethasone 20 mg on the same schedule （group 2）; 37 patients received 1.3 mg/m2 of bortezomib and dexamethasone 40 mg （group 3） and 45 patients received less than 1.3 mg/m2 （0.7-1.0 mg/m2）of bortezomib and dexamethasone 40 mg （group 4）. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Results The median age of groups 1 to 4 was 61,62, 56, and 60 years, respectively. Most patients were in stages Ⅱ/Ⅲ of MM and the most common subtype was IgG The rate of overall response to bortezomib and dexamethasone of group 1 to 4 was 72.2% （13/18）, 73.8% （48/65）, 78.8% （26/33） and 78.0% （32/41） （P=0.91）, including a complete response rate of 22.2% （4/18）, 20.0% （13/65）, 33.3% （11/33） and 29.3% （12/41） （P=0.67）, respectively. There was no statistical significance in time to progression and overall survival among these 4 groups （P 〉0.05）. The most commonly adverse events of any grade in the entire 4 groups were fatigue, gastrointestinal effects, peripheral neuropathy and thrombocytopenia, and there was no significance in the number of adverse events among the 4 groups （P 〉0.05） except that peripheral neuropathy was reported more frequently in group 3 （36.3%） than in group 2 （13.8%, P 〈0.05） and group 4 （14.6%, P〈O.05）.Conclusions The combination of bortezomib and dexamethasone was associated with high responses in Chinese RRMM patients. No significant differences of efficacy were detected in different dose combinations of bortezomib and dexamethasone. Moreover, low dose of bortezomib reduced the incidence of peripheral neuropathy without affecting outcome in the treatment of patients with RRMM in China.展开更多
Background Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma （MM）. Interphase fluorescence in situ hybridization （i-FISH） has been much more effective to identify c...Background Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma （MM）. Interphase fluorescence in situ hybridization （i-FISH） has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique （CC）. To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China. Methods All 672 patients were systematically screened for the following genomic aberrations： del（13q）, IgH rearrangement, del（p53） and lq21 amplifications. Results The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations （48.4%）, -13/13q- （37.6%）, hyperdiploidy （36.6%）, hypodiploidy （30.1%） and IgH rearrangements （23.7%）. The most frequent abnormalities by FISH was del（13q）, which was found in 60.4% patients, whereas IgH rearrangement, lq21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet （P=0.015）, hyperdiploidy was associated with low level of serum albumin （P=0.028）, and IgH rearrangement by FISH was associated with high level of 132 microglobulin （P=0.019）. Moreover, lq21 amplification and del（p53） by FISH conferred a high incidence of progressive disease （PD） after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival （PFS） （P=-0.036）. No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS. Conclusions Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.展开更多
文摘Background Although previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma （RRMM）, the optimal dose combinations of bortezomib and dexamethasone remain unknown. This trial aimed to observe the efficacy and safety of different dose combinations of bortezomib and dexamethasone in the treatment of RRMM patients in China.Methods A total of 168 patients with relapsed multiple myeloma （MM） who were refractory to at lest two prior treatments were enrolled in this multicenter, open-label, non-randomized, prospective clinical trial. Twenty patients received 1.3 mg/m2 of bortezomib twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles and oral or intravenous dexamethasone 20 mg on the day of and after each bortezomib dose （group 1）; 66 patients received less than 1.3 mg/m2（0.7-1.0 mg/m2） of bortezomib and dexamethasone 20 mg on the same schedule （group 2）; 37 patients received 1.3 mg/m2 of bortezomib and dexamethasone 40 mg （group 3） and 45 patients received less than 1.3 mg/m2 （0.7-1.0 mg/m2）of bortezomib and dexamethasone 40 mg （group 4）. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Results The median age of groups 1 to 4 was 61,62, 56, and 60 years, respectively. Most patients were in stages Ⅱ/Ⅲ of MM and the most common subtype was IgG The rate of overall response to bortezomib and dexamethasone of group 1 to 4 was 72.2% （13/18）, 73.8% （48/65）, 78.8% （26/33） and 78.0% （32/41） （P=0.91）, including a complete response rate of 22.2% （4/18）, 20.0% （13/65）, 33.3% （11/33） and 29.3% （12/41） （P=0.67）, respectively. There was no statistical significance in time to progression and overall survival among these 4 groups （P 〉0.05）. The most commonly adverse events of any grade in the entire 4 groups were fatigue, gastrointestinal effects, peripheral neuropathy and thrombocytopenia, and there was no significance in the number of adverse events among the 4 groups （P 〉0.05） except that peripheral neuropathy was reported more frequently in group 3 （36.3%） than in group 2 （13.8%, P 〈0.05） and group 4 （14.6%, P〈O.05）.Conclusions The combination of bortezomib and dexamethasone was associated with high responses in Chinese RRMM patients. No significant differences of efficacy were detected in different dose combinations of bortezomib and dexamethasone. Moreover, low dose of bortezomib reduced the incidence of peripheral neuropathy without affecting outcome in the treatment of patients with RRMM in China.
文摘Background Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma （MM）. Interphase fluorescence in situ hybridization （i-FISH） has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique （CC）. To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China. Methods All 672 patients were systematically screened for the following genomic aberrations： del（13q）, IgH rearrangement, del（p53） and lq21 amplifications. Results The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations （48.4%）, -13/13q- （37.6%）, hyperdiploidy （36.6%）, hypodiploidy （30.1%） and IgH rearrangements （23.7%）. The most frequent abnormalities by FISH was del（13q）, which was found in 60.4% patients, whereas IgH rearrangement, lq21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet （P=0.015）, hyperdiploidy was associated with low level of serum albumin （P=0.028）, and IgH rearrangement by FISH was associated with high level of 132 microglobulin （P=0.019）. Moreover, lq21 amplification and del（p53） by FISH conferred a high incidence of progressive disease （PD） after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival （PFS） （P=-0.036）. No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS. Conclusions Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.
