Risk of kidney toxicity with carfilzomib in multiple myeloma: a meta-analysis of randomized controlled trials
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ORIGINAL ARTICLE
Risk of kidney toxicity with carfilzomib in multiple myeloma: a meta-analysis of randomized controlled trials Somedeb Ball 1 & Tapas Ranjan Behera 2 & Faiz Anwer 2 & Rajshekhar Chakraborty 2 Received: 20 March 2020 / Accepted: 27 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The incidence and relative risk of kidney toxicity with carfilzomib in multiple myeloma (MM) has been incompletely characterized. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing carfilzomibbased with non-carfilzomib-based regimens in MM to investigate the risk of kidney toxicity. Point estimates were pooled in the form of risk ratios (RR) with 95% confidence intervals (CI) using the random-effects model. We identified four RCTs with 2954 patients. The median duration of treatment ranged from 16.3 to 88 weeks in carfilzomib arms. The cumulative rate of kidney toxicities in the carfilzomib arms was 21.3% for all grades and 8.3% for grades 3–5 toxicities, with acute kidney injury being the predominantly reported event. Patients receiving a carfilzomib-based regimen had a significantly higher risk of total kidney toxicity compared with those in the control arms, with pooled RR of 1.79 (95% CI, 1.43–2.23, p < 0.001) and 2.29 (95% CI, 1.59–3.30; p < 0.001), for all grades and grades 3–5 toxicities, respectively. Despite adjustment for the duration of exposure in treatment arms, pooled incidence rate ratios (IRR) for kidney toxicity was significantly increased in the carfilzomib arm compared with control (pooled IRR of 1.28 for all grades and 1.66 for grades 3–5 toxicity). Subgroup analysis based on carfilzomib dose, infusion length, and treatment setting did not identify any significant subgroup effect. Kidney toxicity is an important adverse effect of carfilzomib-based regimens. Prospective studies should investigate patient-, disease-, and treatment-related risk factors for severe kidney toxicities and impact on long-term outcome. Keywords Carfilzomib . Multiple myeloma . Supportive care . Nephrotoxicity . Onconephrology
Introduction Carfilzomib is an irreversible proteasome inhibitor (PI), which binds to the catalytic subunit of 20S proteasome leading to cell cycle arrest and apoptosis [1]. Carfilzomib is primarily metabolized by enzymatic degradation, with the pharmacokinetics being similar across the entire spectrum of kidney impairment [2]. It is widely used in patients with relapsed/refractory mulElectronic supplementary material The online version of this article (https://doi.org/10.1007/s00277-020-04062-x) contains supplementary material, which is available to authorized users. * Rajshekhar Chakraborty [email protected] 1
Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
2
Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA
tiple myeloma (MM) and selected high-risk patients with newly diagnosed MM [3]. Carfilzomib has activity in bort
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