Carfilzomib

Kyprolis is a proteasome inhibitor that 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, or Dexamethasone, or Daratumumab and dexamethasone, or Daratumumab and hyaluronidase-fihj and dexamethasone, or Isatuximab and dexamethasone. as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.

Carfilzomib is a tetrapeptide epoxyketone proteasome inhibitor that irreversibly binds to the N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome. Carfilzomib had antiproliferative and proapoptotic activities in vitro in solid and hematologic tumor cells. In animals, carfilzomib inhibited proteasome activity in blood and tissue and delayed tumor growth in models of multiple myeloma, hematologic, and solid tumors.

Hydrate prior to and following Kyprolis as needed. Premedicate prior to all Cycle 1 doses and if infusion-related reactions develop or reappear. The recommended dosing regimens are as follows. See Full Prescribing Information for additional dosage information. Regimen Dosage Infusion Time Kyprolis and Dexamethasone (Kd) or Kyprolis, Daratumumab and Dexamethasone (DKd) or Kyprolis, Daratumumab and hyaluronidase-fihj and Dexamethasone (DKd) 20/70 mg/m 2 once weekly 30 minutes Kyprolis and Dexamethasone (Kd) or Kyprolis, Daratumumab and Dexamethasone (DKd) or Kyprolis, Daratumumab and hyaluronidase-fihj and Dexamethasone (DKd) or Kyprolis, Isatuximab and Dexamethasone (Isa-Kd) or Kyprolis Monotherapy 20/56 mg/m 2 twice weekly 30 minutes Kyprolis, Lenalidomide and Dexamethasone (KRd) or Kyprolis Monotherapy 20/27 mg/m 2 twice weekly 10 minutes

None. None.

Cardiac Toxicities: Monitor for signs and symptoms of cardiac failure or ischemia. Withhold Kyprolis and evaluate promptly. Acute Renal Failure: Monitor serum creatinine regularly. Tumor Lysis Syndrome (TLS): Administer pre-treatment hydration. Monitor for TLS, including uric acid levels and treat promptly. Pulmonary Toxicity, including Acute Respiratory Distress Syndrome, Acute Respiratory Failure, and Acute Diffuse Infiltrative Pulmonary Disease: Withhold Kyprolis and evaluate promptly. Pulmonary Hypertension: Withhold Kyprolis and evaluate. Dyspnea: For severe or life-threatening dyspnea, withhold Kyprolis and evaluate. Hypertension, including Hypertensive Crisis: Monitor blood pressure regularly. If hypertension cannot be controlled, interrupt treatment with Kyprolis. Venous Thrombosis: Thromboprophylaxis is recommended. Infusion-related Reactions: Premedicate with dexamethasone.

The following clinically significant adverse reactions are described elsewhere in the labeling: Cardiac Toxicities Acute Renal Failure Tumor Lysis Syndrome Pulmonary Toxicity Pulmonary Hypertension Dyspnea Hypertension Venous Thrombosis Infusion-Related Reactions Hemorrhage Thrombocytopenia Hepatic Toxicity and Hepatic Failure Thrombotic Microangiopathy Posterior Reversible Encephalopathy Syndrome Progressive Multifocal Leukoencephalopathy The most common adverse reactions occurring in at least 20% of patients treated with Kyprolis in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.

Unopened vials should be stored refrigerated 2°C to 8°C (36°F to 46°F). Retain in original package to protect from light.