Recommended Treatment Regimens for Carfilzomib (Kyprolis) in Relapsed/Refractory Multiple Myeloma
For patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy, carfilzomib is FDA-approved in combination with lenalidomide and dexamethasone, dexamethasone alone, daratumumab and dexamethasone, daratumumab-hyaluronidase-fihj and dexamethasone, or isatuximab and dexamethasone. 1
FDA-Approved Dosing Regimens
Once Weekly Regimen (30-minute infusion)
- Starting dose: 20 mg/m² on Cycle 1, Day 1
- If tolerated, escalate to 70 mg/m² on Cycle 1, Day 8
- Administer on Days 1,8, and 15 of each 28-day cycle 1
- Approved for use with:
- Dexamethasone (Kd)
- Daratumumab plus dexamethasone (DKd)
- Daratumumab-hyaluronidase-fihj plus dexamethasone (DKd) 1
Twice Weekly Regimen (30-minute infusion)
- Starting dose: 20 mg/m² on Cycle 1, Days 1 and 2
- If tolerated, escalate to 56 mg/m² for subsequent doses
- Administer on Days 1,2,8,9,15, and 16 of each 28-day cycle 1
- Approved for use with:
- Dexamethasone (Kd)
- Daratumumab plus dexamethasone (DKd)
- Daratumumab-hyaluronidase-fihj plus dexamethasone (DKd)
- Isatuximab plus dexamethasone (Isa-Kd) 1
Preferred Combination Regimens
Carfilzomib/Lenalidomide/Dexamethasone (KRd)
- Category 1, preferred option per NCCN guidelines 2
- Based on phase III ASPIRE trial showing:
- Common adverse events include:
- Dyspnea (2.8% vs 1.8% grade ≥3)
- Cardiac failure (3.8% vs 1.8% grade ≥3)
- Hypertension (4.3% vs 1.8% grade ≥3) 2
Carfilzomib/Dexamethasone (Kd)
- Category 1, preferred option per NCCN guidelines 2
- Based on phase III ENDEAVOR trial showing:
- Lower rates of peripheral neuropathy compared to bortezomib (6% vs 32% grade ≥2) 2
- Higher rates of hypertension (15% vs 3% grade ≥3) and dyspnea (6% vs 2% grade ≥3) 2
Other Recommended Regimens
Carfilzomib/Cyclophosphamide/Dexamethasone (KCd)
- Other recommended regimen for relapsed/refractory MM after 1-3 prior therapies 2
- Phase II trials showed:
- Carfilzomib maintenance after KCd showed PFS benefit (11.9 vs 5.6 months) compared to observation 2
Carfilzomib/Pomalidomide/Dexamethasone (KPd)
- Effective in heavily pretreated patients, including those refractory to lenalidomide 4, 5
- Phase 1/2 studies showed:
Special Considerations
Administration Requirements
- Adequate hydration required prior to dosing in Cycle 1
- Oral fluids (30 mL/kg at least 48 hours before Cycle 1, Day 1)
- IV fluids (250-500 mL prior to each dose in Cycle 1) 1
- Premedicate with dexamethasone at least 30 minutes but no more than 4 hours prior to all doses during Cycle 1 1
- Thromboprophylaxis recommended when using carfilzomib in combination with other therapies 1
- Consider antiviral prophylaxis to decrease risk of herpes zoster reactivation 1
Monitoring and Adverse Event Management
- Monitor for cardiac toxicities - most common serious adverse events 1
- Regular monitoring of serum potassium levels 1
- Monitor for thrombocytopenia, which may require dose modifications 1
- Assess for hypertension, which may require treatment interruption if uncontrolled 1
- Monitor renal function regularly 1
Patient Selection Considerations
- Efficacy maintained across age groups, including elderly patients 6
- Prior ASCT should not preclude carfilzomib therapy; patients relapsing after ASCT may have better outcomes 6
- Carfilzomib can be used as a bridge to ASCT with good response rates 6
- Patients with high-risk cytogenetics may benefit from carfilzomib-based regimens 7
Conclusion
Carfilzomib-based regimens offer significant clinical benefit for patients with relapsed/refractory multiple myeloma, with the strongest evidence supporting the combinations of carfilzomib with lenalidomide and dexamethasone (KRd) or with dexamethasone alone (Kd). The choice between once-weekly and twice-weekly dosing, as well as the specific combination partners, should be based on prior therapies, particularly previous exposure and refractoriness to lenalidomide, as well as patient-specific factors such as cardiovascular risk.