What are the effects and efficacy of carfilzomib?

Carfilzomib is a targeted anti-tumor drug, belonging to the class of irreversible proteasome inhibitors, primarily used to treat relapsed or refractory multiple myeloma (RRMM).

Core Mechanism of Action:

Carfilzomib irreversibly binds to the β5 subunit of the 20S proteasome, selectively inhibiting its chymotrypsin-like activity (ChT-L), thereby blocking the degradation of abnormal proteins within tumor cells, leading to protein accumulation, endoplasmic reticulum stress, and ultimately inducing apoptosis in multiple myeloma cells.

Unlike bortezomib, carfilzomib is an epoxy ketone compound, with more stable binding, lower drug resistance, and less neurotoxicity.

Indications:

For adult patients with multiple myeloma whose disease has progressed or relapsed after receiving at least two prior treatment regimens (including proteasome inhibitors such as bortezomib and immunomodulatory agents).

It can be used as a monotherapy or in combination therapy. Common combinations include:

KRd regimen: Carfilzomib + Lenalidomide + Dexamethasone

DKd regimen: Carfilzomib + Daratumumab + Dexamethasone

Kd regimen: Carfilzomib + Dexamethasone (suitable for patients after multiple lines of therapy)

Efficacy:

In a phase III clinical trial in China, the overall response rate (ORR) of carfilzomib combined with dexamethasone reached 35.8%, with a median progression-free survival (PFS) of 5.6 months.

Even in patients resistant to proteasome inhibitors, the objective response rate still reached 32.3%, demonstrating good ability to overcome resistance.

It is listed as a Class I recommendation in the NCCN and CSCO guidelines, suitable for the treatment of patients with first-time relapse.

Usage and Safety:

Administration: Intravenous infusion. The recommended dose is administered twice weekly (days 1, 2, 8, 9, 15, and 16), with each 28-day cycle constituting a single treatment period. The starting dose is 20 mg/m², which can be increased to 27 mg/m² after tolerance is established.

Common adverse reactions (≥30%): Fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, fever, etc.

Careful of serious side effects: Heart failure, pulmonary hypertension, infusion reactions, tumor lysis syndrome, etc. Close monitoring of cardiopulmonary, hepatic, and renal function is necessary during treatment.