Terpos Evangelos, Ntanasis-Stathopoulos Ioannis, Katodritou Eirini, Kyrtsonis Marie-Christine, Douka Vassiliki, Spanoudakis Emmanouil, Papatheodorou Athanasios, Eleutherakis-Papaiakovou Evangelos, Kanellias Nikolaos, Gavriatopoulou Maria, Makras Polyzois, Kastritis Efstathios, Dimopoulos Meletios A
Department of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, PS 11528 Athens, Greece.
Department of Hematology, Theagenio Cancer Hospital, PS 54639 Thessaloniki, Greece.
Cancers (Basel). 2021 Mar 12;13(6):1257. doi: 10.3390/cancers13061257.
Carfilzomib with dexamethasone (Kd) is a well-established regimen for the treatment of relapsed/refractory multiple myeloma (RRMM). There is limited information for the effects of Kd on myeloma-related bone disease. This non-interventional study aimed to assess skeletal-related events (SREs) and bone metabolism in patients with RRMM receiving Kd, in the absence of any bone-targeted agent. Twenty-five patients were enrolled with a median of three prior lines of therapy; 72% of them had evidence of osteolytic bone disease at study entry. During Kd treatment, the rate of new SREs was 28%. Kd produced a clinically relevant (≥30%) decrease in C-telopeptide of collagen type-1 ( = 0.048) and of tartrate-resistant acid phosphatase-5b ( = 0.002) at 2 months. This reduction was at least partially due to the reduction in the osteoclast regulator RANKL/osteoprotegerin ratio, at 2 months ( = 0.026). Regarding bone formation, there was a clinically relevant increase in osteocalcin at 6 months ( = 0.03) and in procollagen type I N-propeptide at 8 months post-Kd initiation. Importantly, these bone metabolism changes were independent of myeloma response to treatment. In conclusion, Kd resulted in a low rate of SREs among RRMM patients, along with an early, sustained and clinically relevant decrease in bone resorption, which was accompanied by an increase in bone formation, independently of myeloma response and in the absence of any bone-targeted agent use.
卡非佐米联合地塞米松（Kd）是一种成熟的复发/难治性多发性骨髓瘤（RRMM）治疗方案。关于Kd对骨髓瘤相关骨病影响的信息有限。这项非干预性研究旨在评估在未使用任何骨靶向药物的情况下，接受Kd治疗的RRMM患者的骨相关事件（SREs）和骨代谢情况。招募了25名患者，他们之前接受治疗的中位数为三线；其中72%在研究开始时存在溶骨性骨病证据。在Kd治疗期间，新SREs的发生率为28%。Kd在2个月时使I型胶原C端肽（P = 0.048）和抗酒石酸酸性磷酸酶-5b（P = 0.002）出现具有临床意义（≥30%）的下降。这种下降至少部分归因于2个月时破骨细胞调节因子核因子κB受体活化因子配体/骨保护素比值的降低（P = 0.026）。关于骨形成，在开始Kd治疗后6个月骨钙素出现具有临床意义的升高（P = 0.03），8个月时I型前胶原N端前肽升高。重要的是，这些骨代谢变化与骨髓瘤对治疗的反应无关。总之，Kd使RRMM患者的SREs发生率较低，同时骨吸收早期、持续且具有临床意义地下降，伴有骨形成增加，这与骨髓瘤反应无关且未使用任何骨靶向药物。
