Abstract: SA-OR005
Carfilzomib-Associated Nephrotoxicity: A Systematic Review and Meta-Analysis
Session Information
- AKI: Onco-Nephrology and Other Drugs
November 09, 2019 | Location: Salon A/B, Walter E. Washington Convention Center
Abstract Time: 05:18 PM - 05:30 PM
Category: Onco-Nephrology
- 1500 Onco-Nephrology
Authors
- Bejjanki, Harini, University of Florida, Gainesville, Florida, United States
- Shah, Chintan, University of Florida, Gainesville, Florida, United States
- Jain, Ankur, University of Florida, Gainesville, Florida, United States
- Bishnoi, Rohit, University of Florida, Gainesville, Florida, United States
- Kazory, Amir, University of Florida, Gainesville, Florida, United States
Background
There has been growing interest in the field of onco-nephrology with the advent of novel antineoplastic treatments, many of which portend nephrotoxic properties. Emergence of proteasome inhibitors (PI) has resulted in significant improvement in survival of patients with multiple myeloma (MM). Carfilzomib (CFZB) is a second-generation PI currently approved for relapsing or refractory MM. We sought to explore whether CFZB is associated with nephrotoxicity (NTX).
Methods
The present review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Articles cited in PubMed, Web of Science, and Clinical Trials Registry, using keywords “Carfilzomib” and “Kyprolis” were searched. A meta-analysis was performed. Cumulative incidence and odds ratios (OR) were calculated using random effect model. We used Common Terminology Criteria for Adverse Events to grade NTX.
Results
A total of 22 studies including 2489 patients were selected. The cumulative incidence of all -grade NTX (grade 1[mild] to grade 5[death]) was 15.5% (CI:11.1-22.1%); high-grade NTX, (grades 3- 5 [life-threatening or resulting in death]) was 4.7 % (CI: 3.3-6.77%). Estimated overall OR of all-grade NTX was 1.81 (CI: 1.09-3.02, p =0.02.). Similarly, the OR of high-grade NTX was 1.85 (CI: 0.93-1.75, p = 0.08). We found no difference in the incidence of all-grade (p =0.38) and high-grade (p = 0.46) NTX between newly diagnosed, relapsing, or refractory MM groups. The high dose of CFZB did not change the incidence of NTX compared to standard dose (p=0.66 and p=0.61 respectively). Similarly, the incidence of NTX was not significantly different when CFZB was used alone or in combination (p=0.63 and p=0.44 respectively). However, concomitant use of immunomodulators significantly increased the incidence of all-grade (p =<0.001), but not high-grade, CFZB-related NTX (p = 0.89).
Conclusion
Currently available data supports the notion that CFZB use is associated with increased risk of NTX. While the risk does not seem to be dose-dependent, it does increase with concomitant use of immunomodulators. Clinicians need to be aware of this complication when considering CFZB use and possibly consider alternative options in patients at risk of renal injury or for those who develop NTX. These results also call for rigorous monitoring of renal function with CFZB use.