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Carfilzomib linked to increased risk for serious infections in multiple myeloma
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ORLANDO — Patients with multiple myeloma treated with carfilzomib demonstrated a significantly higher relative risk for serious infections, particularly respiratory tract infections, compared with those on other treatments, according to a study presented at the ASH Annual Meeting and Exposition.
“Infection is an important cause of morbidity and mortality in multiple myeloma,” Somedeb Ball, MD, from the department of internal medicine at Texas Tech University Health Sciences Center, told HemOnc Today. “Proteasome inhibitors (PI), although they have revolutionized the management, are known to be associated with a risk of infection due to decreased cytotoxic T cell and natural killer cell proliferation, inhibition of dendritic cell function, and suppression of polyclonal immunoglobulins.”
Ball said that while it is unknown whether the potent PI carfilzomib (Kyprolis, Amgen) is associated with higher odds of viral infection, there are concerns.
To determine the risk for serious infections with carfilzomib for multiple myeloma, Ball and colleagues conducted a systematic review and meta-analysis of four randomized controlled trials, specifically ASPIRE, ENDEAVOR, FOCUS and CLARION. The analysis included 2,954 patients with multiple myeloma, mainly relapsed/refractory disease; 1,486 received treatment with carfilzomib and 1,468 were controls. In all the studies, patients received carfilzomib twice weekly at doses ranging from 20/27 to 20/56 mg/m². The duration of treatment ranged from a median of 16 to 88 weeks.
The FOCUS trial evaluated single-agent carfilzomib, whereas all the other trials assessed combination regimens, including carfilzomib-dexamethasone, carfilzomib-lenalidomide-dexamethasone, and carfilzomib-melphalan-prednisone.
Results indicated that compared with other agents, carfilzomib-based regimens significantly increased the relative risk for total serious infections (pooled RR, 1.4; 95% CI, 1.17-1.69). Respiratory tract infections attributed to 65% of all serious infections in the carfilzomib group, of which 38% were serious pneumonia.
While patients who received carfilzomib-based treatments had a significantly greater risk for serious respiratory tract infections, compared with those receiving other therapeutic regimens (pooled RR, 1.3; 95% CI, 1.12-1.5), the occurrence of serious pneumonia among the carfilzomib and control arms did not significantly differ (pooled RR, 1.14; 95% CI, 0.92–1.41).
There was no statistically significant subgroup effect based on treatment dose or setting.
“These findings will assist clinicians with a risk-benefit assessment prior to the initiation of carfilzomib-based regimens,” Ball said. “Future studies should investigate patient-related and disease-related risk factors for serious infections and the utility of prophylactic antibiotic or intravenous immunoglobulin in high-risk patients.” – by Alaina Tedesco
Reference:
Ball S, et al. Abstract 1841. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2019; Orlando.
Disclosure: Ball reports no relevant financial disclosures.