Tatekoshi Ayumi, Sato Tsutomu, Ibata Soushi, Hashimoto Akari, Kamihara Yusuke, Horiguchi Hiroto, Ono Kaoru, Takada Kohichi, Iyama Satoshi, Takimoto Rishu, Kobune Masayoshi, Kato Junji
Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine.
Rinsho Ketsueki. 2014 Nov;55(11):2271-6.
To date, intravenous drip infusion of zoledronic acid (ZA) has mainly been used for the treatment and prevention of skeletal-related events (SRE) in patients with multiple myeloma (MM). Recently, denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL), has also become available for the same purpose, but little is known about the impact of switching from ZA to denosumab. Herein, we present a retrospective study on bone metabolic markers in 10 MM patients initially treated with ZA and then switched to denosumab. Consequently, the levels of bone resorption markers, tartrate-resistant acid phosphatase 5b (TRACP-5b) and serum type-I collagen crosslinked N-telopeptide (sNTX), significantly decreased after denosumab treatment, while the levels of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), showed no apparent changes. No patient developed severe hypocalcemia with denosumab treatment. In one patient not given chemotherapy, the M-protein level increased after switching from ZA to denosumab and plateaued when ZA was restarted. Based on this finding, we anticipate that switching from ZA to denosumab would exert a stronger suppressive effect on osteoclasts, but the anti-myeloma activity of ZA must be taken into consideration.
迄今为止，静脉滴注唑来膦酸（ZA）主要用于治疗和预防多发性骨髓瘤（MM）患者的骨相关事件（SRE）。最近，一种完全人源化的抗核因子κB受体活化剂配体（RANKL）单克隆抗体地诺单抗也已用于相同目的，但对于从ZA转换为地诺单抗的影响知之甚少。在此，我们对10例最初接受ZA治疗后转而使用地诺单抗的MM患者的骨代谢标志物进行了一项回顾性研究。结果，地诺单抗治疗后，骨吸收标志物抗酒石酸酸性磷酸酶5b（TRACP-5b）和血清I型胶原交联N-端肽（sNTX）水平显著降低，而骨形成标志物骨钙素（OC）和骨特异性碱性磷酸酶（BAP）水平无明显变化。地诺单抗治疗期间，无患者发生严重低钙血症。在1例未接受化疗的患者中，从ZA转换为地诺单抗后M蛋白水平升高，重新使用ZA后趋于平稳。基于这一发现，我们预计从ZA转换为地诺单抗对破骨细胞的抑制作用更强，但必须考虑ZA的抗骨髓瘤活性。
