Table 5.

Clinical practice recommendations for carfilzomib10,22,23

		Emory approach
Prophylaxis
Hydration • Reduces the risk of renal toxicity and TLS	• Instruct the patient to drink 8 cups of water a day during dosing • 250–500 mL of normal saline should be administered before and after infusion (as needed)	• Use 500 mL normal saline before and after infusion, except in patients at risk for fluid overload (renal, cardiac) where 250 mL volumes are employed
Subtherapeutic dexamethasone • Prevents or alleviates flu-like infusion symptoms	• 4 mg (PO or IV) should be administered before infusion during Cycle 1 with the 20 mg/m2 starting dose and before all doses during the first cycle of the target dose of 27 mg/m2	• Use 4 mg before the dose for all infusions except when contraindicated
Allopurinol • Reduces the risk of renal toxicity and TLS	• 100–300 mg PO daily	• Used selectively in patients with high tumor burden (eg, elevated LDH, uric acid, >50% plasma cells on bone marrow examination)
Antivirals (eg, acyclovir, famciclovir, valaciclovir) • Prevents herpes virus infections	• Antiviral agent should be prescribed in patients at risk • Common regimen is acyclovir 400 mg PO BID	• Acyclovir 400 mg PO BID in all patients
Antibacterials (eg, ciprofloxacin, cotrimoxazole, levofloxacin, moxifloxacin) • Prevents infections related to immunosuppression, particularly in patients at risk of certain infections	• Appropriate antibacterial agent should be prescribed in patients at risk	• Co-trimoxazole double strength PO daily MWF in all patients except when contraindicated
Management of AEs
Hematologic toxicity	• Withhold the dose of carfilzomib	• Assess drug versus disease causes
Neutropenia (grade 3/4)  Thrombocytopenia (grade 4)	• If the patient fully recovers before the next scheduled dose, continue at same dose level  ○ Thrombocytopenia: if the patient recovers to grade 3 thrombocytopenia, reduce dose by one dose level  ○ Neutropenia: if the patient recovers to grade 2 neutropenia, reduce the dose by one dose levela • If tolerated, the reduced dose may be escalated to the previous dose at the discretion of the physician	• Hold carfilzomib if ANC <1,000/mm3, platelets <25,000/mm3
Cardiac toxicity  Grade 3/4 cardiac toxicity; new onset or worsening of congestive heart failure, decreased left ventricular function, or myocardial ischemia	• Withhold the dose of carfilzomib until the event resolves or returns to baseline • After resolution, consider whether the patient should restart at a reduced dosea • If reduced dose is tolerated, the dose may be escalated to the previous dose at the discretion of the physician	• Per product information
Pulmonary hypertension or Peripheral neuropathy (grade 3/4)	• Withhold the dose of carfilzomib until the event resolves or returns to baseline • Restart at the dose used before the event or reduce dosea at the discretion of the physician • If reduced dose is tolerated, the dose may be escalated to the previous dose at the discretion of the physician	• Per product information
Pulmonary complications (grade 3/4) or Other grade 3/4 nonhematologic toxicities	• Withhold the dose of carfilzomib until the event resolves or returns to baseline • Consider restarting at the next scheduled treatment with one dose level reductiona • If reduced dose is tolerated, the dose may be escalated to the previous dose at the discretion of the physician	• Per product information
Hepatic toxicity Grade 3/4 elevation of transaminases, bilirubin, or other liver abnormalities	• Withhold the dose of carfilzomib until the event resolves or returns to baseline • After resolution, consider if restarting carfilzomib is appropriate • If appropriate, reinitiate at a reduced dosea with frequent monitoring of liver function • If reduced dose is tolerated, the dose may be escalated to the previous dose at the discretion of the physician	• Hold for AST/ALT >5 times the ULN and bilirubin >3 times ULN • Assess other potential causes • Reinitiate following resolution per product information
Renal toxicity Serum creatinine ≥2× baseline	• Withhold the dose of carfilzomib until renal function recovers to grade 1 or to baseline; monitor renal function • If renal dysfunction is attributable to carfilzomib, restart the next scheduled treatment at a reduced dosea • If renal dysfunction is not attributable to carfilzomib, restart at the dose used before the event • If reduced dose is tolerated, the dose may be escalated to the previous dose at the discretion of the physician	• Assess cause and timing of renal insult • If stabilized, clearly due to myeloma, and early in treatment, consider continuing at same carfilzomib dose • Avoid concurrent nephrotoxins when possible, particularly in first two cycles

Note:

^aFrom carfilzomib 27 mg/m² to 20 mg/m² or from carfilzomib 20 mg/m² to 15 mg/m².

Abbreviations: AE, adverse event; ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; BID, twice daily; IV, intravenously; LDH, lactate dehydrogenase; MWF, Monday, Wednesday, Friday; PO, orally; TLS, tumor lysis syndrome; ULN, upper limit of normal.