Abstract
Simple SummaryCarfilzomib with dexamethasone is an important therapeutic option for patients with relapsed/refractory multiple myeloma. We sought to evaluate the effect of this regimen on the bone-related outcomes, which are associated with both quality of life and survival. Among 25 patients, less than one third experienced a new skeletal-related event during treatment, even in the absence of any bone-targeted agent. Interestingly, there was a significant decrease in serum biomarkers of bone resorption, which was at least partially due to the sRANKL/OPG ratio reduction. Furthermore, Kd produced an increase in markers of bone formation. Importantly, these changes were independent of myeloma response to treatment. Therefore, the combination of carfilzomib and dexamethasone improves bone metabolism and bone health in patients with advanced multiple myeloma.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 (p = 0.048) and of tartrate-resistant acid phosphatase-5b (p = 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 (p = 0.026). Regarding bone formation, there was a clinically relevant increase in osteocalcin at 6 months (p = 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.
Highlights
Bone disease is a cardinal feature of multiple myeloma (MM) and it is attributed to the deregulation of the fine tuning between bone formation and bone resorption [1]
Treatment of myeloma bone disease is primarily based on bone-targeting agents such as bisphosphonates and denosumab [4], anti-myeloma regimens including proteasome inhibitors seem to exert a beneficial effect on bone metabolism as well [5,6,7,8,9,10,11,12]
Materials and Methods This was an open-label, prospective, non-interventional, multicenter study aiming to evaluate the effect of Kd combinations in skeletal-related events (SREs) and bone indices in patients with refractory multiple myeloma (RRMM), in the absence of any bone-targeted agent, who were treated in five myeloma centers in Greece
Summary
Bone disease is a cardinal feature of multiple myeloma (MM) and it is attributed to the deregulation of the fine tuning between bone formation and bone resorption [1]. Treatment of myeloma bone disease is primarily based on bone-targeting agents such as bisphosphonates and denosumab [4], anti-myeloma regimens including proteasome inhibitors seem to exert a beneficial effect on bone metabolism as well [5,6,7,8,9,10,11,12]. Carfilzomib with dexamethasone (Kd) is a well-established regimen for patients with relapsed/refractory multiple myeloma (RRMM) in the clinical practice [17,18,19]. Clinical data on the net effects of carfilzomib on indices of bone metabolism are limited [5,20]
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