Carfilzomib Treatment for Multiple Myeloma

Efficacy and Safety

Carfilzomib in combination with lenalidomide and dexamethasone (KRd) significantly improved progression-free survival (PFS) compared to lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma: 26.3 months with KRd vs 17.6 months with Rd (HR 0.69; p=0.0001), as recommended by the European Medicines Agency and the National Comprehensive Cancer Network 1, 2
Carfilzomib in combination with dexamethasone (Kd) significantly improved PFS compared to bortezomib with dexamethasone (Vd) in patients with relapsed/refractory multiple myeloma: 18.7 months with Kd vs 9.4 months with Vd (HR 0.53; p<0.0001), with an overall response rate (ORR) of 77% with Kd vs 63% with Vd, as noted by the American Society of Clinical Oncology 1, 2
The KRd regimen also reduced the risk of death by 21%, resulting in approximately 8 months of additional overall survival, with an ORR of 87.1% with KRd vs 66.7% with Rd 1, 2

The standard dosage of carfilzomib is 20 mg/m² on days 1, 2, 8, 9, 15, and 16 of cycle 1, increasing to 27 mg/m² on the same days for cycle 2 and subsequent cycles in monotherapy or with dexamethasone, as approved by the FDA 1, 2
Carfilzomib is administered as an intravenous infusion over 2-10 minutes, and should be administered after hemodialysis in patients with end-stage renal disease (ESRD) 1, 3

Common adverse events associated with carfilzomib include hypertension (12.2% all grades, 4.3% grade ≥3), heart failure (4.1% all grades, 2.5% grade ≥3), cardiac ischemia (1.8% all grades), anemia, and thrombocytopenia (24.9% grade ≥3), with a lower incidence of peripheral neuropathy (6-13% all grades) compared to bortezomib (32%) 1, 2
The incidence of cardiovascular events was 18.1% (all grades) and 8.2% (grade ≥3), with the most common events being hypertension, heart failure, and ischemic heart disease 2

A detailed cardiovascular evaluation is recommended to identify patients at risk of cardiovascular adverse events, and close monitoring of blood pressure before and during treatment is necessary, as recommended by the European Network of Myeloma and the Italian Society of Arterial Hypertension 2
The European Society of Medical Oncology and the National Comprehensive Cancer Network recommend close monitoring of cardiovascular toxicity during treatment with carfilzomib 1, 2

The National Comprehensive Cancer Network, European Society for Medical Oncology, American Society of Clinical Oncology, and International Myeloma Society recommend carfilzomib in combination with lenalidomide and dexamethasone (KRd) as a category 1 preferred regimen for first relapse, and carfilzomib with dexamethasone (Kd) as an effective alternative with less neurotoxicity 1, 3, 4, 2
Carfilzomib + cyclophosphamide + dexamethasone (KCd) is an option for patients refractory to lenalidomide, and carfilzomib is being evaluated for the treatment of newly diagnosed multiple myeloma, with ongoing studies investigating combinations of carfilzomib with monoclonal antibodies, such as daratumumab and isatuximab 4, 2