地舒单抗与唑来膦酸治疗新诊断多发性骨髓瘤骨病的疗效及安全性

Analysis of the efficacy and safety of bone disease treatment in patients with newly diagnosed multiple myeloma treated with denosumab or zoledronic acid

目的探讨地舒单抗(DENOS)与唑来膦酸(ZOL)治疗新诊断多发性骨髓瘤骨病(MBD)的疗效及安全性。方法回顾性分析2021年3月1日至2023年6月30日解放军总医院第五医学中心血液病医学部收治的80例新诊断MBD患者的临床资料。18例伴重度肾损害(SRI)患者[内生肌酐清除率(CrCl)<30 ml/min]均接受DENOS治疗,62例非SRI患者分为DENOS组(30例)和ZOL组(32例)。结果80例MBD患者中26例(33%)发生低钙血症,22例发生于第1次用药后。非SRI患者中DENOS组低钙血症发生率高于ZOL组[20%(6/30)对13%(4/32),P=0.028],SRI患者低钙血症发生率为89%(16/18)。多因素分析显示,CrCl<30 ml/min与DENOS治疗后低钙血症相关(P<0.001)。抗骨吸收药物治疗1个月后,DENOS组SRI、非SRI患者血清Ⅰ型胶原交联羧基端肽β特殊序列降低率大于ZOL组(68%对59%对27%,P<0.001),DENOS组SRI、非SRI患者血清Ⅰ型原胶原氨基端前肽升高率大于ZOL组(34%对20%对11%,P<0.05)。抗骨吸收药物治疗后各组全段甲状旁腺激素升高。所有患者均未发生抗骨吸收药物相关颌骨坏死及肾脏不良事件,各组血液学总有效率、完全缓解率、严格意义的完全缓解率差异均无统计学意义(P值均>0.05),中位无进展生存及总生存时间均未达到。结论DENOS治疗MBD具有较强的抗骨吸收作用和低肾毒性,低钙血症是常见不良反应,多为轻中度且可控。

Objective This study investigated the efficacy and safety of denosumab(DENOS)versus zoledronic acid(ZOL)in the bone disease treatment of newly diagnosed multiple myeloma.Methods The clinical data of 80 patients with myeloma bone disease(MBD)at the Fifth Medical Center of PLA General Hospital between March 1,2021 and June 30,2023 were retrospectively reviewed.Eighteen patients with severe renal impairment(SRI,endogenous creatinine clearance rate<30 ml/min)were treated with DENOS,and 62 non-SRI patients were divided into DENOS(30 patients)and ZOL group(32 patients).Results Hypocalcemia was observed in 26(33%)patients,and 22 patients developed hypocalcemia during the first treatment course.The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group[20%(6/30)vs 13%(4/32),P=0.028].The incidence of hypocalcemia in SRI was 89%(16/18).Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration(P<0.001).After 1 month of antiresorptive(AR)drug application,the decrease in the serumβ-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group(68%vs 59%vs 27%,P<0.001).The increase in serum procollagen typeⅠN-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group(34%vs 20%vs 11%,P<0.05).The level of intact parathyroid hormone in each group increased after AR drug treatment.None of the patients developed osteonecrosis of the jaw and renal adverse events,and no statistically significant differences in the overall response rate,complete remission and stringent complete remission rates were found among the groups(P>0.05),and the median PFS and OS time were not reached(P>0.05).Conclusions In the treatment of MBD,DENOS minimizes nephrotoxicity and has strong AR effect.Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.