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）. T展开更多
G蛋白偶联受体,C类5组成员D(G-protein-coupled receptor family C group 5 member D,GPRC5D)被认为是多发性骨髓瘤(multiple myeloma,MM)免疫治疗的潜在靶标。2021年9月1日—2022年3月23日,本Ⅱ期单臂临床试验共纳入33例复发/难治(rela...G蛋白偶联受体,C类5组成员D(G-protein-coupled receptor family C group 5 member D,GPRC5D)被认为是多发性骨髓瘤(multiple myeloma,MM)免疫治疗的潜在靶标。2021年9月1日—2022年3月23日,本Ⅱ期单臂临床试验共纳入33例复发/难治(relapsed or refractory,R/R)MM患者(18~70岁),在接受淋巴细胞清除化疗后输注2×106/kg抗GPRC5D嵌合抗原受体(chimeric antigen receptor,CAR)-T细胞,随后进行有效性和安全性的评估。在中位随访5.2(3.2~8.9)个月时,患者总体反应率为91%(95%CI 76%~98%,30/33例),包括11例(33%)严格意义上的完全缓解,10例(30%)完全缓解,4例(12%)非常好的部分缓解和5例(15%)部分缓解。9例既往接受过抗B细胞成熟抗原(B-cell maturation antigen,BCMA)CAR-T细胞治疗的患者疗效均达部分缓解或以上,其中包括2例接受过2次或以上抗BCMA CAR-T细胞输注的患者。3级或更高的血液学毒性为中性粒细胞减少[33例(100%)]、贫血[17例(52%)]和血小板减少症[15例(45%)]。33例患者中25例(76%)发生细胞因子释放综合征(均为1级或2级),3例患者发生神经毒性(1例2级和1例3级免疫效应细胞相关神经毒性综合征,1例3级头痛)。综上所述,抗GPRC5D CAR-T细胞疗法在R/R MM患者中表现出令人鼓舞的临床疗效和可控的安全性。对于抗BCMA CAR-T细胞治疗后进展或无效的MM患者,抗GPRC5D CAR-T细胞治疗可能是一种潜在的替代选择。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）. T
文摘G蛋白偶联受体,C类5组成员D(G-protein-coupled receptor family C group 5 member D,GPRC5D)被认为是多发性骨髓瘤(multiple myeloma,MM)免疫治疗的潜在靶标。2021年9月1日—2022年3月23日,本Ⅱ期单臂临床试验共纳入33例复发/难治(relapsed or refractory,R/R)MM患者(18~70岁),在接受淋巴细胞清除化疗后输注2×106/kg抗GPRC5D嵌合抗原受体(chimeric antigen receptor,CAR)-T细胞,随后进行有效性和安全性的评估。在中位随访5.2(3.2~8.9)个月时,患者总体反应率为91%(95%CI 76%~98%,30/33例),包括11例(33%)严格意义上的完全缓解,10例(30%)完全缓解,4例(12%)非常好的部分缓解和5例(15%)部分缓解。9例既往接受过抗B细胞成熟抗原(B-cell maturation antigen,BCMA)CAR-T细胞治疗的患者疗效均达部分缓解或以上,其中包括2例接受过2次或以上抗BCMA CAR-T细胞输注的患者。3级或更高的血液学毒性为中性粒细胞减少[33例(100%)]、贫血[17例(52%)]和血小板减少症[15例(45%)]。33例患者中25例(76%)发生细胞因子释放综合征(均为1级或2级),3例患者发生神经毒性(1例2级和1例3级免疫效应细胞相关神经毒性综合征,1例3级头痛)。综上所述,抗GPRC5D CAR-T细胞疗法在R/R MM患者中表现出令人鼓舞的临床疗效和可控的安全性。对于抗BCMA CAR-T细胞治疗后进展或无效的MM患者,抗GPRC5D CAR-T细胞治疗可能是一种潜在的替代选择。
