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Peptide

Carfilzomib (Kyprolis)

Carfilzomib is a second-generation tetrapeptide epoxyketone proteasome inhibitor for multiple myeloma. FDA-approved 2012 (monotherapy), expanded 2015-2016 (combinations). ASPIRE Phase 3 (n=792): PFS 26.3 vs 17.6 months with KRd vs Rd (HR 0.69, P<0.001). OS improved to 48.3 vs 40.4 months. ENDEAVOR: PFS 18.7 vs 9.4 months vs bortezomib (HR 0.53). SAFETY: Significant cardiac toxicity - heart failure (4-16%), hypertension (9-27%), thromboembolism (24%). Requires cardiac monitoring.

Research notice. This page is for education and research. Peptides may not be FDA-approved for human use and may only be legally available for research. Talk to a qualified clinician before considering any peptide.

Best evidence
Grade A
Conditions studied
1
Outcomes
13
Graded outcomes
5251

Evidence by condition

  • Strong
  • Moderate
  • Limited
  • Very limited

1 condition, plus general outcomes

Multiple Myeloma

Multiple Myeloma: outcomes studied for Carfilzomib (Kyprolis)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Cardiac Toxicity

SAFETY CONCERN: Heart failure 4-16%, hypertension 9-27%, arrhythmias, QT prolongation (ROR 4.9). FDA FAERS: 38.6% cardiomyopathy-related, 22.7% cardiac failure. Requires baseline cardiac assessment and monitoring.

Worsens (the measure goes up)Moderate effect33 studies

Studies that measured cardiac toxicity

and 23 more in the citations list

Progression-Free Survival (KRd)

ASPIRE (n=792): Median PFS 26.3 months with KRd vs 17.6 months with Rd (HR 0.69, P<0.001). 8.7 month improvement. Deep responders (≥CR) achieved 50.4 months PFS.

Improves (the measure goes up)Large effect32 studies

Studies that measured progression-free survival (krd)

and 22 more in the citations list

Overall Survival

ASPIRE final analysis: OS 48.3 vs 40.4 months (HR 0.79, P=0.0045). 7.9 month survival benefit. ENDEAVOR vs bortezomib also showed OS advantage.

Improves (the measure goes up)Moderate effect32 studies

Studies that measured overall survival

and 22 more in the citations list

PFS vs Bortezomib

ENDEAVOR (n=929): Median PFS 18.7 vs 9.4 months with Kd vs Vd (HR 0.53, P<0.0001). Nearly doubled PFS. Establishes superiority over first-generation proteasome inhibitor.

Improves (the measure goes up)Large effect32 studies

Studies that measured pfs vs bortezomib

and 22 more in the citations list

Thromboembolism

SAFETY CONCERN: 24% embolic/thrombotic events in FAERS database. DVT prophylaxis recommended. Higher risk than bortezomib. Consider in patients with cardiovascular risk factors.

Worsens (the measure goes down)Moderate effect31 studies

Studies that measured thromboembolism

and 21 more in the citations list

General

General: outcomes studied for Carfilzomib (Kyprolis)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Safety/Tolerability

12 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes up)Moderate effect29 studies

Studies that measured safety/tolerability

and 19 more in the citations list

Pulmonary Function

8 human trials support this finding. Human clinical trial data available.

Improves (the measure goes up)Moderate effect27 studies

Studies that measured pulmonary function

and 17 more in the citations list

Anti-Cancer Activity

7 systematic reviews and preclinical studies support this finding. Evidence includes systematic reviews/meta-analyses. Primarily preclinical evidence.

Improves (the measure goes up)Small effect26 studies

Studies that measured anti-cancer activity

and 16 more in the citations list

Cancer Cell Apoptosis

3 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect24 studies

Studies that measured cancer cell apoptosis

and 14 more in the citations list

Immune Function

3 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect22 studies

Studies that measured immune function

and 12 more in the citations list

Blood Pressure

3 human trials support this finding. Human clinical trial data available.

Improves (the measure goes down)Small effect22 studies
Kidney Function

3 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes up)Small effect22 studies
Liver Protection

2 systematic reviews and preclinical studies support this finding. Evidence includes systematic reviews/meta-analyses. Primarily preclinical evidence.

Improves (the measure goes up)Small effect21 studies

Key findings

  • Cardiac ToxicityMultiple MyelomaWorsens (the measure goes up)
  • Progression-Free Survival (KRd)Multiple MyelomaImproves (the measure goes up)
  • Overall SurvivalMultiple MyelomaImproves (the measure goes up)

Safety notes in the studies

  • Higher risk than bortezomib.
  • Consider in patients with cardiovascular risk factors.

Studies cited

60 studies from PubMed

  1. Cancer targeting carfilzomib nanomedicine: a comprehensive review of delivery vehicles and efficacy.Nanomedicine (London, England), 2025 · PMID 41159240
  2. Health-Related Quality of Life in Patients With Relapsed/Refractory Multiple Myeloma Treated With Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone: An Analysis of Patient-Reported Outcomes From the Phase 3 CANDOR Trial.Clinical lymphoma, myeloma & leukemia, 2025 · PMID 40087058
  3. Carfilzomib-lenalidomide-dexamethasone versus lenalidomide-dexamethasone in patients with newly diagnosed myeloma ineligible for autologous stem-cell transplantation (EMN20): a randomised, open-label, multicentre, phase 3 trial.The Lancet. Haematology, 2025 · PMID 40769686
  4. Carfilzomib suppressed LDHA-mediated metabolic reprogramming by targeting ATF3 in esophageal squamous cell carcinoma.Biochemical pharmacology, 2024 · PMID 38000560
  5. Carfilzomib activates ER stress and JNK/p38 MAPK signaling to promote apoptosis in hepatocellular carcinoma cells.Acta biochimica et biophysica Sinica, 2024 · PMID 38591121
  6. HIV-protease inhibitors potentiate the activity of carfilzomib in triple-negative breast cancer.British journal of cancer, 2024 · PMID 38969867
  7. Characteristics and outcomes of patients developing pulmonary hypertension associated with proteasome inhibitors.The European respiratory journal, 2024 · PMID 38697649
  8. An open-label phase 2 study treating patients with first or second relapse of multiple myeloma with carfilzomib, pomalidomide, and dexamethasone (KPd): SELECT study.Leukemia & lymphoma, 2024 · PMID 38497533
  9. Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly-diagnosed multiple myeloma: A systematic review and meta-analysis.American journal of hematology, 2024 · PMID 38606993
  10. Isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple myeloma (IKEMA): overall survival analysis of a phase 3, randomised, controlled trial.The Lancet. Haematology, 2024 · PMID 39067465
  11. Carfilzomib-induced thrombotic microangiopathy (TMA) refractory to eculizumab: A case report and literature review.Annals of hematology, 2024 · PMID 39191958
  12. Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review.Blood cancer journal, 2024 · PMID 39511171
  13. Carfilzomib-induced life-threatening lung injury in refractory multiple myeloma.Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2023 · PMID 37489075
  14. Lactoferrin ameliorates carfilzomib-induced renal and pulmonary deficits: Insights to the inflammasome NLRP3/NF-κB and PI3K/Akt/GSK-3β/MAPK axes.Life sciences, 2023 · PMID 37926296
  15. Canagliflozin mitigates carfilzomib-induced endothelial apoptosis via an AMPK-dependent pathway.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2023 · PMID 37247463
  16. Carfilzomib-induced Thrombotic Microangiopathy: A Case Based Review.Hematology/oncology and stem cell therapy, 2023 · PMID 32735793
  17. Carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone as maintenance therapy after autologous stem-cell transplantation in patients with multiple myeloma (ATLAS): interim analysis of a randomised, open-label, phase 3 trial.The Lancet. Oncology, 2023 · PMID 36642080
  18. Carfilzomib modulates tumor microenvironment to potentiate immune checkpoint therapy for cancer.EMBO molecular medicine, 2022 · PMID 34898004
  19. Efficacy and toxicity of carfilzomib- or bortezomib-based regimens for treatment of transplant-ineligible patients with newly diagnosed multiple myeloma: A meta-analysis.Medicine, 2022 · PMID 36181088
  20. Efficacy and safety of carfilzomib for the treatment of multiple myeloma: An overview of systematic reviews.Critical reviews in oncology/hematology, 2022 · PMID 36244642
  21. An Untargeted Metabolomics Approach on Carfilzomib-Induced Nephrotoxicity.Molecules (Basel, Switzerland), 2022 · PMID 36432029
  22. Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma: A randomised phase 2 trial by the Nordic Myeloma Study Group.European journal of haematology, 2022 · PMID 34536308
  23. Carfilzomib-induced thrombotic microangiopathy is underestimated in clinical practice: A report of five patients and literature review.Leukemia & lymphoma, 2022 · PMID 35373680
  24. Efficacy and safety profile of deep responders to carfilzomib-based therapy: a subgroup analysis from ASPIRE and ENDEAVORLeukemia, 2021 · PMID 33067574
  25. Carfilzomib Promotes the Unfolded Protein Response and Apoptosis in Cetuximab-Resistant Colorectal Cancer.International journal of molecular sciences, 2021 · PMID 34281166
  26. Fatal pulmonary toxicity following Carfilzomib administration.Acute medicine, 2021 · PMID 35072387
  27. Incidence and Management of Carfilzomib-induced Cardiovascular Toxicity; A Systematic Review and Meta-analysis.Cardiovascular & hematological disorders drug targets, 2021 · PMID 33845729
  28. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial.Lancet (London, England), 2021 · PMID 34097854
  29. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomised, open-label, phase 2 trial.The Lancet. Oncology, 2021 · PMID 34774221
  30. Carfilzomib-Induced Pulmonary Hypertension.American journal of therapeutics, 2020 · PMID 31724976
  31. Risk of kidney toxicity with carfilzomib in multiple myeloma: a meta-analysis of randomized controlled trials.Annals of hematology, 2020 · PMID 32382772
  32. Venetoclax in combination with carfilzomib and dexamethasone in relapsed/refractory multiple myeloma harboring t(11,14)(q13;q32): two case reports and a review of the literature.Journal of medical case reports, 2020 · PMID 32321588
  33. Infection risk with carfilzomib in multiple myeloma: a systematic review and meta-analysis of randomised controlled trials.British journal of haematology, 2020 · PMID 32400886
  34. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study.Lancet (London, England), 2020 · PMID 32682484
  35. Carfilzomib with immunomodulatory drugs for the treatment of newly diagnosed multiple myeloma.Leukemia, 2019 · PMID 31341235
  36. Apremilast ameliorates carfilzomib-induced pulmonary inflammation and vascular injuries.International immunopharmacology, 2019 · PMID 30500623
  37. [Efficacy and Safety of Carfilzomib in the Treatment of Multiple Myeloma：A Systematic Evaluation].Zhongguo shi yan xue ye xue za zhi, 2019 · PMID 31839055
  38. Carfilzomib: A Tale of a Heartbreaking Moment: Case Report and Concise Review of the Literature.Cardiovascular & hematological disorders drug targets, 2019 · PMID 30516116
  39. Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple MyelomaJ Clin Oncol, 2018 · PMID 29341834
  40. Carfilzomib-Associated Cardiovascular Adverse Events: A Systematic Review and Meta-analysisJAMA Oncol, 2018 · PMID 29285538
  41. Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trialsBlood Adv, 2018 · PMID 29991494
  42. Carfilzomib in relapsed or refractory multiple myeloma patients with early or late relapse following prior therapy: A subgroup analysis of the randomized phase 3 ASPIRE and ENDEAVOR trialsHematol Oncol, 2018 · PMID 29446103
  43. Cardiotoxicity associated with carfilzomib: systematic review and meta-analysis.Leukemia & lymphoma, 2018 · PMID 29465266
  44. Efficacy and toxicity profile of carfilzomib based regimens for treatment of multiple myeloma: A systematic review.Critical reviews in oncology/hematology, 2018 · PMID 29650268
  45. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study.The Lancet. Oncology, 2018 · PMID 29866475
  46. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trialLancet Oncol, 2017 · PMID 28843768
  47. Proteasome inhibitor-induced gastrointestinal toxicity.Current opinion in supportive and palliative care, 2017 · PMID 28333868
  48. Carfilzomib/pomalidomide single-agent or in combination with other agents for the management of relapsed/refractory multiple myeloma: a meta-analysis of 37 trials.Oncotarget, 2017 · PMID 27458170
  49. Carfilzomib-containing combinations as frontline therapy for multiple myeloma: A meta-analysis of 13 trials.European journal of haematology, 2017 · PMID 28295593
  50. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre studyLancet Oncol, 2016 · PMID 26671818
  51. Management of Carfilzomib-Associated Cardiac Adverse EventsClin Lymphoma Myeloma Leuk, 2016 · PMID 26907720
  52. Fatal pulmonary toxicity due to carfilzomib (Kyprolis™).Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2016 · PMID 26044587
  53. Carfilzomib reverses pulmonary arterial hypertension.Cardiovascular research, 2016 · PMID 26952044
  54. A practical review on carfilzomib in multiple myeloma.European journal of haematology, 2016 · PMID 26893241
  55. Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma.Targeted oncology, 2016 · PMID 26972294
  56. Efficacy of carfilzomib in the treatment of relapsed and (or) refractory multiple myeloma: a meta-analysis of data from clinical trials.Discovery medicine, 2016 · PMID 27875670
  57. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myelomaN Engl J Med, 2015 · PMID 25482145
  58. Carfilzomib-associated tumor lysis syndrome.Pharmacotherapy, 2014 · PMID 24390940
  59. Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studiesHaematologica, 2013 · PMID 23935022
  60. Second generation proteasome inhibitors: carfilzomib and immunoproteasome-specific inhibitors (IPSIs).Current cancer drug targets, 2011 · PMID 21247387