蛋白酶体抑制剂同类药物转换对初治多发性骨髓瘤患者疗效和预后的影响

Effects of in-class transition of proteasome inhibitors on curative efficacy and prognosis of newly-treated patients with multiple myeloma

目的探讨蛋白酶体抑制剂(PI)硼替佐米同类药物转换为伊沙佐米治疗初治多发性骨髓瘤(MM)患者的有效性和安全性。方法回顾性分析2018年1月至2020年12月深圳市第二人民医院收治的63例初治MM患者临床资料,分为转换组(23例)和硼替佐米组(40例),两组均以含硼替佐米的方案为一线治疗方案,转换组患者因不耐受硼替佐米不良反应转换为伊沙佐米,硼替佐米组患者未进行药物转换。比较两组患者疗效及无进展生存(PFS)的差异。结果转换组患者进行同类药物转换前总有效率(ORR)为95.7%(22/23),≥非常好的部分缓解(VGPR)率为52.2%(12/23);转换后ORR为95.7%(22/23),≥VGPR率为82.6%(19/23);硼替佐米组ORR为90.0%(36/40),≥VGPR率为72.5%(29/40),两组患者ORR及≥VGPR率比较差异均无统计学意义(χ^(2)=0.64,P=0.424;χ^(2)=0.82,P=0.364)。转换组接受PI治疗的中位周期数为9个,中位PFS时间未达到;硼替佐米组接受PI治疗的中位周期数为7.5个,中位PFS时间为30.0个月(95%CI 19.1~40.9个月),两组PFS差异无统计学意义(P=0.275)。硼替佐米组中,12例因不良反应停用硼替佐米,其中位PFS时间20.0个月(95%CI 12.6~27.4个月),转换组与硼替佐米组停用PI患者的PFS比较,差异有统计学意义(P=0.043)。转换组患者发生周围神经病变21例(21/23,91.3%),≥3级不良反应的发生率为13.0%(3/23);硼替佐米组发生周围神经病变22例(22/40,55.0%),≥3级不良反应的发生率为12.5%(5/40)。结论对于初治MM患者,硼替佐米转换为伊沙佐米能提高缓解深度,减少因停用PI导致的复发。

Objective To explore the efficacy and safety of in-class transition from proteasome inhibitor bortezomib to ixazomib in the treatment of newly-treated patients with multiple myeloma(MM).Methods The clinical data of 63 newly-treated MM patients in Shenzhen Second People's Hospital from January 2018 to December 2020 were retrospectively analyzed.They were divided into transition group(23 cases)and bortezomib group(40 cases).Both groups were treated with bortezomib-containing regimen as the first-line treatment regimen.In case of intolerable adverse reactions,patients in the transition group were treated with ixazomib instead of bortezomib,while the patients in the bortezomib group did not undergo drug transition.The curative effect and progression-free survival(PFS)were compared between the two groups.Results In the transition group,the overall response rate(ORR)before in-class transition was 95.7%(22/23),the rate of≥very good partial remission(VGPR)was 52.2%(12/23);the ORR after transition was 95.7%(22/23),and the rate of≥VGPR was 82.6%(19/23).In the bortezomib group,ORR was 90.0%(36/40),and the rate of≥VGPR was 72.5%(29/40).There was no significant difference in ORR and the rate of≥VGPR between the two groups(χ^(2)=0.64,P=0.424;χ^(2)=0.82,P=0.364).The median number of cycles of PI therapy in the transition group was 9,and the median PFS time was not reached.The median number of cycles of PI therapy in the bortezomib group was 7.5,and the median PFS time was 30.0 months(95%CI 19.1-40.9 months),there was no significant difference in PFS between the two groups(P=0.275).In the bortezomib group,12 patients discontinued bortezomib due to adverse reactions,the median PFS time was 20.0 months(95%CI 12.6-27.4 months),and the PFS of patients who discontinued PI in the transition group and the bortezomib group was compared,the difference was statistically significant(P=0.043).In the transition group,21 patients(21/23,91.3%)developed peripheral neuropathy,and the incidence of≥grade 3 adverse reactions was 13.0%(3/23);in the bortezomib group,22 patients(22/40,55.0%)developed peripheral neuropathy,and the incidence of≥grade 3 adverse reactions was 12.5%(5/40).Conclusions For newly-treated MM patients,the transition from bortezomib to ixazomib can improve the depth of remission and reduce the recurrence caused by the discontinuation of PI.