Summary

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• Kyprolis (carfilzomib) is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with lenalidomide and dexamethasone, in combination with dexamethasone, in combination with daratumumab and dexamethasone, in combination with daratumumab and hyaluronidase-fihj and dexamethasone, as a single agent for patients who have received one or more lines of therapy, and in combination with Isatuximab and dexamethasone.
• This summary is based on the review of 10 systematic reviews/meta-analyses. ^[1-10]
• Overall Response Rate (ORR) and Progression-Free Survival (PFS): Carfilzomib-based treatments demonstrated higher ORRs compared to bortezomib/dexamethasone and lenalidomide/dexamethasone, with a median PFS of 22.5 months in combination with lenalidomide and dexamethasone (KRd) versus 29.8 months for daratumumab with lenalidomide and dexamethasone (DaraRd). However, carfilzomib did not consistently improve PFS or overall survival (OS) compared to other treatments like daratumumab.
• Efficacy in Specific Populations: Carfilzomib showed a PFS improvement in patients with +1q cytogenetic abnormality and was effective in frail patients with a median PFS of 24.1 months (KRd27) and 18.7 months (Kd56). However, in transplant-ineligible patients, carfilzomib-based regimens, while achieving higher ORR, did not significantly improve PFS or OS compared to bortezomib-based regimens.
• Comparison with Other Treatments: Daratumumab-based regimens were often superior to carfilzomib in both ORR and PFS, with better overall survival outcomes. Carfilzomib generally showed higher ORR compared to bortezomib but did not outperform it in terms of PFS and OS.
• Cardiotoxicity and Kidney Toxicity: Carfilzomib was associated with a significantly increased risk of high-grade cardiovascular events (OR 2.68) and kidney toxicity (RR 1.79 for all grades; 2.29 for grades 3-5) compared to controls.
• Non-Hematological Toxicity: Carfilzomib-based regimens had a higher incidence of grade 3-4 non-hematological toxicities, including dyspnea, hypertension, acute kidney injury, and heart failure, compared to other treatments such as daratumumab-based regimens.
• Subgroup Findings: Carfilzomib demonstrated improved progression-free survival (PFS) in patients with +1q cytogenetic abnormality and showed consistent efficacy and safety in frail patients, including those with higher comorbidities and reduced performance status. However, in transplant-ineligible patients, while carfilzomib-based regimens had higher overall response rates (ORR), they did not improve PFS or overall survival (OS) compared to bortezomib-based regimens. Carfilzomib was also effective in lenalidomide-refractory patients, especially in combination with monoclonal antibodies.