Kyprolis

Multiple myeloma — in combination with dexamethasone or with lenalidomide plus dexamethasone, in patients who have received one to three prior lines of therapy; in combination with daratumumab, dexamethasone in patients who have received one to three prior lines of therapy

With lenalidomide + dex (28-day cycle): 20 mg/m² IV Days 1, 2 of Cycle 1; then 27 mg/m² Days 8, 9, 15, 16; subsequent cycles 27 mg/m² Days 1, 2, 8, 9, 15, 16
With dex only (28-day cycle): 20 mg/m² IV Days 1, 2 of Cycle 1; then 56 mg/m² subsequent doses Days 8, 9, 15, 16
Infusion time: 10 min (20 mg/m²), 30 min (27 or 56 mg/m²)
Hydration: 250-500 mL NS IV before and after dose in Cycle 1

For injection: 10 mg, 30 mg, 60 mg lyophilized powder in single-dose vials

None listed.

• Cardiac Toxicities: New onset or worsening heart failure (7%), decreased LVEF, myocardial ischemia and infarction. Withhold for Grade 3-4 cardiac events.
• Pulmonary Toxicity: Acute respiratory distress syndrome (ARDS), acute respiratory failure, acute diffuse infiltrative pulmonary disease. Discontinue for Grade 3-4.
• Pulmonary Hypertension: Reported in up to 2% of patients.
• Dyspnea: 28% incidence (Grade 3: 5%).
• Hypertension: 22% including hypertensive crisis. Monitor BP regularly.
• Venous Thromboembolic Events: DVT and PE reported. Thromboprophylaxis recommended.
• Infusion Reactions: Including life-threatening. Pre-medicate with dexamethasone.
• Hemorrhage: Fatal and serious including GI, intracranial, and pulmonary hemorrhage.
• Thrombocytopenia: 36% (Grade 4: 10%). Monitor platelets frequently.
• Hepatotoxicity: Cases of hepatic failure reported. Monitor LFTs.
• TLS: Monitor patients with high tumor burden.
• PRES: Discontinue if suspected.

Anemia (47%), fatigue (33%), thrombocytopenia (36%), nausea (32%), diarrhea (33%), dyspnea (28%), pyrexia (27%), upper respiratory tract infection (24%), headache (22%), hypertension (22%), cough (21%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Carfilzomib is an irreversible proteasome inhibitor that selectively and irreversibly binds to the N-terminal threonine-containing active sites of the 20S proteasome (chymotrypsin-like activity). Unlike bortezomib which is reversible, carfilzomib's irreversible binding provides sustained proteasome inhibition. This leads to accumulation of polyubiquitinated proteins, activating the unfolded protein response, cell cycle arrest, and apoptosis in myeloma cells.

Half-life: approximately 1 hour (on Day 1 of Cycle 1). Rapidly and extensively metabolized via peptidase cleavage and epoxide hydrolysis. Less than 1% excreted unchanged in urine. Clearance: 263 L/h.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• ASPIRE — Carfilzomib + lenalidomide/dex vs. lenalidomide/dex in relapsed MM. Phase III, n=792.
  🔬 NCT01080391 ↗ 📄 Primary Publication ↗
• ENDEAVOR — Carfilzomib + dex vs. bortezomib + dex in relapsed MM. Phase III, n=929.
  🔬 NCT01568866 ↗ 📄 Primary Publication ↗

Kyprolis has FDA-approved indications across the following cancer types covered on PipelineEvidence: