Carfilzomib comes under the brand name Kyprolis. It acts by inhibiting the proteasome. The proteasome is a system within the cells that breaks down proteins when they are damaged or no longer required. By preventing the breakdown of proteins in cancer cells, which are more likely to contain more abnormal proteins, the carfilzomib injection causes the destruction (death) of cancer cells.
Carfilzomib is aimed to treat adult patients with multiple myeloma (MM) who have had at least one previous treatment for this disease. Multiple myeloma is a cancer of plasma cells (a type of white blood cell). Carfilzomib will be prescribed to you together with daratumumab and dexamethasone, with lenalidomide and dexamethasone, or only with dexamethasone. Dexamethasone, daratumumab, and lenalidomide are other medications used in order to treat multiple myeloma.
Warnings/Precautions:
Cardiac Toxicity: Patients with normal baseline ventricular function, and also those with pre-existing cardiac conditions have experienced cardiac failure, myocardial ischemia, restrictive cardiomyopathy, and infarction, including fatalities, throughout the course of carfilzomib injection treatment. A death because of cardiac arrest was noted within 1-day of administration. Rates of cardiac failure were greater in the carfilzomib containing arms of studies evaluating KRd vs. Rd (6 vs. 4%) and Kd vs. Vd (8 vs. 3%).
Acute Renal Failure: AEs involving renal insufficiency have been reported in ~ 10 percent of patients treated with carfilzomib. Acute renal failure was noted more often in those with advanced relapsed/refractory myeloma who took carfilzomib monotherapy. The risk was higher in those with decreased baseline estimated creatinine clearance.
Tumor Lysis Syndrome (TLS): Some cases of tumor lysis syndrome, including fatalities, have been noted. Those with an increased tumor burden should be considered at the greatest risk.
Pulmonary Toxicity: Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary diseases such as pneumonitis and interstitial lung disease have been observed in less than one percent of those taking carfilzomib therapy. Certain cases have been fatal.
Pulmonary Hypertension: PAH (Pulmonary Arterial Hypertension) has been noted in ~ 1 percent of treated patients. Grade-3 or greater pulmonary arterial hypertension has been observed in < 1 percent.
Dyspnea: Dyspnea was noted in 28 percent of patients treated with carfilzomib therapy (Grade-3 or greater in 4 percent). Assess to exclude cardiopulmonary conditions.
Hypertension including Hypertensive Crisis & Hypertensive Emergency: Severe hypertensive episodes have been reported with carfilzomib treatment and some cases have been fatal.
Infusion reactions: Reactions can appear promptly after or up to 24 hours following administration of carfilzomib injection. Symptoms include chills, fever, arthralgia, facial flushing, myalgia, facial edema, vomiting, shortness of breath, weakness, hypotension, syncope, chest tightness, or angina. Certain reactions have been life-threatening.
Thrombocytopenia: The platelet nadirs are typically noted between Day 8'th and 15'th of each 28-day cycle with recovery usually by the initiation of the next cycle. Thrombocytopenia was noted in ~ 40 percent of patients in clinical trials.
Hepatic Toxicity and Failure: Some cases of hepatic failure have been noted (<1 percent) during carfilzomib treatment. The serum transaminases may also be increased by the therapy of carfilzomib.
Thrombotic Microangiopathy: Cases of thrombotic microangiopathy, including TTP/HUS (Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome) have been noted; some events have been fatal.
Posterior reversible encephalopathy syndrome (PRES): Posterior reversible encephalopathy syndrome has been observed. Patients may present with headache, seizure, lethargy, blindness, confusion, altered consciousness, and other visual/neurologic disturbances, alone with HTN. Diagnosis is confirmed by neuroradiological imaging. Discontinue carfilzomib therapy if posterior reversible encephalopathy syndrome is suspected and evaluated.
Embryo-fetal Toxicity: On behalf of its mechanism of action and findings in animals, it is suspected that the carfilzomib therapy can be responsible for causing fetal harm if administered to a pregnant woman.