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Carfilzomib is a second-generation proteasome inhibitor with less nerve damage but more heart and blood-pressure effects.
Carfilzomib is an epoxyketone that irreversibly binds the beta5 subunit of the proteasome, giving deeper inhibition than bortezomib with much less peripheral neuropathy. In ENDEAVOR, carfilzomib-dexamethasone (Kd) beat bortezomib-dexamethasone (Vd) with PFS 18.7 versus 9.4 months and an OS benefit, underpinning its 2015 approvals after the 2012 accelerated approval in relapsed disease. It is used in KRd and in Isa-Kd and Dara-Kd combinations, mainly in relapsed disease, because ENDURANCE showed no frontline advantage of KRd over VRd in standard-risk patients. The trade-off is cardiovascular: hypertension in 25%, cardiac failure in 5% and dyspnoea in 28% in ENDEAVOR, so blood pressure and cardiac function are monitored. Amgen develops it. It is a stronger proteasome inhibitor that spares the nerves but asks more of the heart.
Ball-and-stick model from PubChem 2D record (no 3D conformer available). PubChem record
Epoxyketone that irreversibly binds the β5 proteasome subunit.
1.Carfilzomib slips into a pocket on its target.
Given by infusion or injection in a clinic or hospital outpatient department, so it is a Part B drug: Medicare pays 80% after the Part B deductible and the patient owes 20% coinsurance, uncapped in Original Medicare unless a Medigap policy applies. HCPCS J9047.
Covered under the medical benefit with prior authorisation confirming diagnosis, biomarker status and line of therapy; site-of-care policies may steer infusions away from hospital outpatient departments.
20% Part B coinsurance on a high-cost infusion adds up quickly: Medigap Plan G or N, Medicare Advantage maximum out-of-pocket, Medicaid dual eligibility, or a charity fund are the usual buffers.
Sources: Medicare.gov: Chemotherapy · Medicare.gov: Prescription drugs (outpatient, Part B). Not medical or financial advice; verify with your plan.
Sources: NICE TA457 · SMC advice: carfilzomib. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
Multiple myeloma after at least 2 prior therapies including bortezomib and an immunomodulatory agent and disease progression on or within 60 days of completion of the last therapy
Accelerated approval on a surrogate endpoint, with a confirmatory trial required.
Multiple myeloma after at least 2 prior therapies including bortezomib and an immunomodulatory agent and disease progression on or within 60 days of completion of the last therapy
Confirmed: the accelerated approval of 2012 converted to traditional approval 3.5 years after it was granted.
| Region | Year | Indication |
|---|---|---|
| US | 2012 | Relapsed myeloma (accelerated) |
| US | 2015 | With lenalidomide-dexamethasone; with dexamethasone (ENDEAVOR) |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Hypertension | 25% | 9% |
| Cardiac failure | - | 5% |
| Dyspnoea | 28% | - |
ENDEAVOR. Events listed without rates were not read from a primary source; see the label. Blank cells mean the figure was not sourced, not that it is zero.
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Query for this drug: (TITLE:"Carfilzomib" OR ABSTRACT:"Carfilzomib" OR TITLE:"Kyprolis" OR ABSTRACT:"Kyprolis") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Carfilzomib, not a curated reading list.
Shares A Study of Daratumumab, A Study Comparing AZD0120, a Dual-targeted CAR-T Against B-cell Maturation Antigen (BCMA) and CD19, Versus Standard Regimens in Participants With Rela, A Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Standard of Care in Participants With Relapsed-Refractory Mult, Study Assessing Activity of Intravenous (IV) Etentamig Monotherapy Versus Standard Available Therapies in Adult Participants With Relapsed or Refracto.
Shares A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Multiple Myeloma Receiving T Cell Engaging Bi/Tri-spe, A Study to Evaluate Mezigdomide in Combination With Carfilzomib and Dexamethasone (MeziKD) Versus Carfilzomib and Dexamethasone (Kd) in Participants W, A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Tre, Ubiquitin-proteasome system & protein homeostasis.
Shares Sundar Jagannath, Proteasome (PSMB5), Aaron Ciechanover, A Study Comparing AZD0120, a Dual-targeted CAR-T Against B-cell Maturation Antigen (BCMA) and CD19, Versus Standard Regimens in Participants With Rela.
Shares A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Multiple Myeloma Receiving T Cell Engaging Bi/Tri-spe, A Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With Multiple, Ubiquitin-proteasome system & protein homeostasis, Relapsed or refractory multiple myeloma.
Shares Study Assessing Activity of Intravenous (IV) Etentamig Monotherapy Versus Standard Available Therapies in Adult Participants With Relapsed or Refracto, A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Tre, MagnetisMM-32: A Study to Learn About the Study Medicine Called Elranatamab in People With Multiple Myeloma (MM) That Has Come Back After Taking Other, Multiple myeloma.
Shares A Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With Multiple, A Study to Evaluate Mezigdomide in Combination With Carfilzomib and Dexamethasone (MeziKD) Versus Carfilzomib and Dexamethasone (Kd) in Participants W, A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Tre, Relapsed or refractory multiple myeloma.
Shares A Study of Daratumumab, A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Multiple Myeloma Receiving T Cell Engaging Bi/Tri-spe, A Study to Investigate Subcutaneous Isatuximab in Combination With Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory, A Study Comparing AZD0120, a Dual-targeted CAR-T Against B-cell Maturation Antigen (BCMA) and CD19, Versus Standard Regimens in Participants With Rela.
Shares A Study of Daratumumab, A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Multiple Myeloma Receiving T Cell Engaging Bi/Tri-spe, A Study Comparing AZD0120, a Dual-targeted CAR-T Against B-cell Maturation Antigen (BCMA) and CD19, Versus Standard Regimens in Participants With Rela, A Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With Multiple.