Evidence Grade A — Regulatory approved. 1807 published studies. 271 registered clinical trials.
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Carfilzomib (sold as Kyprolis) is an intravenous cancer treatment for multiple myeloma that has come back after previous therapy. Like bortezomib, it works by blocking the cell's protein recycling system, but carfilzomib binds permanently rather than temporarily, which may contribute to its stronger anti-cancer effect in some settings.
Carfilzomib is also known by these brand and alternate names:
1,807 published studies: 1356 human, 47 animal, 224 in-vitro, 423 reviews
Carfilzomib is marketed as Kyprolis (approved July 2012) for relapsed or refractory multiple myeloma. It is administered intravenously on a twice-weekly schedule in combination with other agents.
In the ENDEAVOR trial, the carfilzomib-dexamethasone combination nearly doubled progression-free survival compared to bortezomib-dexamethasone (18.7 versus 9.4 months). The ASPIRE trial showed that adding carfilzomib to lenalidomide-dexamethasone extended overall survival by approximately 8 months. Cardiovascular toxicity (heart failure, hypertension) is the most significant side effect and requires cardiac monitoring. The intravenous-only administration and twice-weekly schedule are practical limitations compared to oral proteasome inhibitors now in development.
Cells contain a structure called the proteasome that breaks down old, damaged, or excess proteins — acting as the cell's recycling system. Myeloma cells produce enormous quantities of antibody proteins and are especially dependent on this system to avoid being overwhelmed by protein waste. Carfilzomib permanently disables the proteasome's main cutting site by forming an irreversible chemical bond, causing toxic proteins to accumulate until the cell self-destructs. Its irreversible binding distinguishes it from the older bortezomib, which binds reversibly.
Carfilzomib's evidence is strong. The ENDEAVOR trial showed that carfilzomib nearly doubled the time before disease worsened compared to bortezomib (18.7 versus 9.4 months) in patients with relapsed myeloma. The ASPIRE trial demonstrated an overall survival benefit of approximately 8 months when carfilzomib was added to a standard two-drug regimen. The most significant concern is cardiovascular toxicity — heart failure and hypertension occur at clinically meaningful rates, requiring cardiac monitoring during treatment. The grade 3 or higher adverse event rate is around 80%, reflecting that this is an intensive cancer treatment. The twice-weekly IV schedule is also a practical burden for patients. Research continues into frontline use and subcutaneous formulation development that could ease the administration burden.
PeptideTrace tracks 271 registered clinical trials for Carfilzomib sourced from ClinicalTrials.gov.
Carfilzomib Multiple Myeloma Expanded Access Protocol for Patients With Relapsed and Refractory Disease
Testing the Investigational Medication Combination of Daratumumab and Teclistamab Compared to the Usual Treatment (Daratumumab, Pomalidomide, Dexamethasone or Daratumumab, Carfilzomib, Dexamethasone) for Patients With High-risk Multiple Myeloma Refractory or in First Relapse
Study of Selinexor With Carfilzomib, Isatuximab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma
Testing an Experimental Approach to Treat Patients With Plasma Cell Leukemia, The QUANTUM Trial
Cevostamab in Combination With Pomalidomide and Dexamethasone Versus Standard of Care in Participants With Previously Treated Multiple Myeloma
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Carfilzomib is a tetrapeptide epoxyketone proteasome inhibitor, MW 719.91 Da. Synthetic analogue of epoxomicin. Epoxyketone pharmacophore forms irreversible morpholino adduct with N-terminal Thr of proteasome catalytic subunit. Unlike bortezomib's reversible mechanism. IV over 10-30 min on consecutive-day schedules in 28-day cycles. Half-life ~1 hour.
Irreversibly binds beta-5 (chymotrypsin-like) catalytic subunit of 20S proteasome via epoxyketone warhead forming dual covalent morpholino adduct with Thr-1. >10-fold selectivity over off-target proteases. Proteasome inhibition accumulates misfolded proteins, activating unfolded protein response, ER stress, and apoptosis in myeloma cells.
Marketed as Kyprolis. Approved July 20, 2012. ENDEAVOR (N=929): PFS 18.7 vs. 9.4 months vs. bortezomib (HR 0.53, P<0.0001). ASPIRE (N=792): KRd vs. Rd PFS 26.3 vs. 17.6 months (HR 0.69); OS 48.3 vs. 40.4 months (HR 0.79). Indications: relapsed/refractory multiple myeloma after 1-3 prior lines.
Zilucoplan is marketed as Zilbrysq (approved October 2023) for anti-acetylcholine receptor antibody-positive generalised myasthenia gravis in adults. Administered as a daily subcutaneous self-injection. In the RAISE trial, zilucoplan showed statistically significant improvements in both activities of daily living and quantitative muscle strength scores compared to placebo, with improvements evident from week one. Its key differentiator from existing complement inhibitors (eculizumab, ravulizumab) is the self-injectable format — those alternatives require hospital-based intravenous infusions. As with all complement inhibitors, patients require meningococcal vaccination before starting treatment due to increased susceptibility to meningococcal infection.
Vancomycin is marketed as Vancocin and Firvanq (approved 1958, with oral solution Firvanq approved 2018). It is the standard treatment for serious MRSA infections (bloodstream infections, endocarditis, pneumonia, bone infections) and is first-line for severe C. difficile colitis. Vancomycin requires therapeutic drug monitoring — blood levels must be checked regularly to ensure the dose is effective without causing kidney damage or hearing loss. The rise of vancomycin-resistant enterococci (VRE) and occasional vancomycin-intermediate S. aureus (VISA) strains represent ongoing challenges. Despite being nearly 70 years old, vancomycin remains irreplaceable for many serious infections, though newer alternatives like daptomycin and the lipoglycopeptides offer advantages in specific settings.
Bortezomib is marketed as Velcade (approved May 2003) for multiple myeloma and mantle cell lymphoma. Generic versions are available. Originally given intravenously, subcutaneous injection is now preferred as it causes significantly less nerve damage. The VISTA trial established bortezomib-based combination therapy as standard for newly diagnosed myeloma patients ineligible for transplant, with median time to disease progression of 24 months versus 16.6 months with older chemotherapy. Peripheral neuropathy (numbness and tingling in hands and feet) is the main dose-limiting side effect, affecting up to 30% of patients. Bortezomib transformed myeloma from a disease with a median survival of approximately 3 years to one where many patients live a decade or more with sequential treatments.
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