Efficacy and toxicity profile of carfilzomib based regimens for treatment of multiple myeloma: A systematic review

Abstract

Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone. Extensive literature search identified a total of 1839 articles. Twenty-six articles (n = 5980) met the inclusion criteria, 15 in newly diagnosed multiple myeloma (NDMM) and 11 in RRMM group. CFZ demonstrates comparable or even better efficacy to bortezomib with much favorable AE profile. Deep, rapid and sustainable response using KRd with safer toxicity profile supports extension of KRd therapy to frontline therapy for all risk categories of MM. High incidence of grade ≥3 HTN underscores the importance of serial BP monitoring. In RRMM, CFZ has documented efficacy with standard 20-27mg/m2 dose. Further large-scale trials are needed to study benefit-to-risk profile of 20-56 and 20-70 mg/m2 dose of CFZ vs standard 20-27 mg/m2 dose in NDMM and RRMM.

Peripheral nervous system involvement in lymphomas

“…Carfilzomib, a second-generation proteasome inhibitor approved for multiple myeloma treatment, shares similar adverse effects with bortezomib, but has been reported to be less neurotoxic. 119 Lenalidomide, a thalidomide analogue with immune-modulating and anti-angiogenetic activities, shows a better safety profile when compared with its precursor, especially regarding neurotoxicity. 120 Lenalidomide has also been successfully used in patients with POEMS syndrome.…”

Vancomycin Intoxication and Cefepime-induced Encephalopathy Treated by Abdominal Drainage of Massive Ascites in Addition to Online Hemodiafiltration

“…Fourth, lenalidomide-related encephalopathy was not ruled out. Lenalidomide-related neurological and psychiatric disorders, such as headache, dizziness, tremor, peripheral neuropathy, or anxiety may occur, although consciousness disorder is a rare complication (19)(20)(21)(22)(23)(24)(25)(26)(27). Ischemic stroke and progressive multifocal leukoencephalopathy are reported to be lenalidomide-related encephalopathies detectable with head MRI (28,29).…”

Carfilzomib-induced tumor lysis syndrome in relapsed multiple myeloma: a report of two cases

“…6 It has been shown that deep, rapid, and sustainable responses can be obtained with carfilzomib-based combinations. 7 Carfilzomib, inducing more rapid and deeper responses, is associated with a higher risk of TLS compared with other drugs that act more slowly. Two Phase II studies and one phase I/II study of carfilzomib in relapsed/ refractory MM reported TLS incidence as 0.4%, 1%, and 2.7%, respectively.…”