INDICATIONS
Indications
  • KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone, or with lenalidomide plus dexamethasone, or with daratumumab plus dexamethasone, or with daratumumab plus hyaluronidase-fihj plus dexamethasone, or with isatuximab plus dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.Read More
  • KYPROLIS® is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.Close
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Kd:

KYPROLIS® + dexamethasone

Superior efficacy in a proteasome inhibitor1,2

Kd offers superior efficacy in a proteasome inhibitor with nearly 19 months mPFS1,2

ENDEAVOR trial: Kd vs Vd

Phase 3, randomized, open-label superiority study: (N = 929) comparing Kd 56 mg/m2 twice weekly to Vd in relapsed or refractory multiple myeloma patients who had received 1 to 3 prior lines of therapy. The primary endpoint was PFS. Select secondary endpoints included OS, ORR, DoR, and safety.1,2

19-months-mPFS
kd-progress-chart-desktop

CI, confidence interval; DoR, depth of response; Kd, carfilzomib + dexamethasone; HR, hazard ratio; mPFS, median progression-free survival; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; Vd, bortezomib + dexamethasone.

Kd treatment yielded deeper, more durable responses2

CR, complete response; Kd, carfilzomib + dexamethasone; ORR, overall response rate; PR, partial response; Vd, bortezomib + dexamethasone;
VGPR, very good partial response.

Exploratory post hoc subgroup analysis for specific patient populations

PFS results with Kd were consistent regardless of prior bortezomib exposure1,*

analysis-bortezomib-exposure-graph
analysis-bortezomib-graph

*Study was not powered for PFS efficacy in either subgroup, and estimation of PFS in these subgroups was not a study objective.

CI, confidence interval; HR, hazard ratio; Kd, carfilzomib + dexamethasone; mPFS, median progression-free survival; PFS, progression-free survival;
Vd, bortezomib + dexamethasone.

Study Design

Kd vs Vd in RRMM (ENDEAVOR)

Kd vs Vd in RRMM ENDEAVOR study design

Phase 3, randomized, open-label superiority study: (N=929) comparing Kd 56 mg/m2 twice weekly to Vd in relapsed or refractory multiple myeloma patients who had received 1 to 3 prior lines of therapy. The primary endpoint was PFS. Select secondary endpoints included OS, ORR, DoR, and safety.1,2

Study schema1,2

Key eligibility criteria (N = 929):

  • Adults with relapsed or refractory MM
  • 1 to 3 prior treatments
  • ECOG PS 0-2
  • Prior KYPROLIS® or bortezomib allowed if:
    • ≥ PR to prior treatment
    • ≥ 6 months without PI
    • Not discontinued due to toxicity
  • LVEF ≥ 40%
  • CrCl ≥ 15 mL/min

Key exclusion criteria:

  • Grade 3 or 4 peripheral neuropathy (or Grade 2 with pain) ≤ 14 days prior to randomization
  • Myocardial infarction ≤ 4 months prior to randomization
  • NYHA Class III or IV heart failure†
  • < PR to all prior regimens

*Patient stratification included prior proteasome inhibitor therapy (either bortezomib or carfilzomib, or no prior therapy); prior lines of therapy (1 vs 2 or 3); International Staging System stage (1 vs 2 or 3); and planned route of bortezomib administration, if randomized to the bortezomib group (intravenous vs subcutaneous).

†NYHA classification of heart failure III is defined as: Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea (shortness of breath). IV is defined as: Unable to carry out any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.

BIW, twice a week; CrCI, creatinine clearance; DoR, depth of response; ECOG PS, Eastern Cooperative Oncology Group Performance Status; Kd, carfilzomib and dexamethasone; LVEF, left ventricular ejection fraction; MM, multiple myeloma; NYHA, New York Heart Association; ORR, overall response rate; OS, overall survival;
PFS, progression-free survival; PI, proteasome inhibitor; PR, partial response; R, randomization; Vd, bortezomib and dexamethasone.

  • Patient Demographics and Baseline Characteristics2

    (View data)

    Baseline disease characteristics and prior treatments were balanced between study arms

    *The high-risk group consisted of patients with the genetic subtypes t(4;14) or t(14;16) in 10% or more of screened plasma cells, or deletion 17p in 20% or more of screened plasma cells based on central review of bone marrow samples obtained at study entry. The standard-risk group consisted of patients without these genetic subtypes.1

    †Two patients in the Vd arm had four prior regimens.2

    ‡Refractory = disease not achieving a minimal response or better, progressing during therapy, or progressing within 60 days after completion of therapy.2

    IMiD, immunomodulatory agent; ISS, International Staging System.

SafetySafety

Safety

Learn more about Kd safety information
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Dosing

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Kd, carfilzomib + dexamethasone.

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IMPORTANT SAFETY INFORMATION FOR KYPROLIS®

Cardiac Toxicities

  • New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS®. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of administration.
  • Monitor patients for signs or symptoms of cardiac failure or ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS® for Grade 3 or 4 cardiac adverse reactions until recovery, and consider whether to restart at 1 dose level reduction based on a benefit/risk assessment.
  • While adequate hydration is required prior to each dose in Cycle 1, monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate.
  • For patients ≥ 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment prior to starting treatment with KYPROLIS® and remain under close follow-up with fluid management.

Acute Renal Failure

  • Cases of acute renal failure, including some fatal renal failure events, and renal insufficiency (including renal failure) have occurred. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS® monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.

Tumor Lysis Syndrome

  • Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred. Patients with a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly, and withhold until resolved.

Pulmonary Toxicity

  • Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue KYPROLIS®.

Pulmonary Hypertension

  • Pulmonary arterial hypertension (PAH) was reported. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS® for PAH until resolved or returned to baseline and consider whether to restart based on a benefit/risk assessment.

Dyspnea

  • Dyspnea was reported in patients treated with KYPROLIS®. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop KYPROLIS® for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart based on a benefit/risk assessment.

Hypertension

  • Hypertension, including hypertensive crisis and hypertensive emergency, has been observed, some fatal. Control hypertension prior to starting KYPROLIS®. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS® and evaluate. Consider whether to restart based on a benefit/risk assessment.

Venous Thrombosis

  • Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed. Provide thromboprophylaxis for patients being treated with the combination of KYPROLIS® with dexamethasone or with lenalidomide plus dexamethasone or with daratumumab and dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.
  • For patients using hormonal contraception associated with a risk of thrombosis, consider an alternative method of effective contraception during treatment.

Infusion-Related Reactions

  • Infusion-related reactions, including life-threatening reactions, have occurred. Signs and symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, laryngeal edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration. Premedicate with dexamethasone to reduce the incidence and severity of infusion-related reactions.

Hemorrhage

  • Fatal or serious cases of hemorrhage have been reported. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate.

Thrombocytopenia

  • KYPROLIS® causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Monitor platelet counts frequently during treatment. Reduce or withhold dose as appropriate.

Hepatic Toxicity and Hepatic Failure

  • Cases of hepatic failure, including fatal cases, have occurred. KYPROLIS® can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate.

Thrombotic Microangiopathy

  • Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome, have occurred. Monitor for signs and symptoms of TTP/HUS. Discontinue if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS® may be restarted. The safety of reinitiating KYPROLIS® is not known.

Posterior Reversible Encephalopathy Syndrome (PRES)

  • Cases of PRES have occurred in patients receiving KYPROLIS®. If PRES is suspected, discontinue and evaluate with appropriate imaging. The safety of reinitiating KYPROLIS® is not known.

Progressive Multifocal Leukoencephalopathy (PML)

  • Cases of PML, including fatal cases, have occurred. In addition to KYPROLIS®, other contributary factors may include prior or concurrent use of immunosuppressive therapy. Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms. If PML is suspected, discontinue and initiate evaluation for PML including neurology consultation.

Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-ineligible Patients

  • In a clinical trial of transplant-ineligible patients with newly diagnosed multiple myeloma comparing KYPROLIS®, melphalan, and prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher incidence of serious and fatal adverse reactions was observed in patients in the KMP arm. KMP is not indicated for transplant-ineligible patients with newly diagnosed multiple myeloma.

Embryo-fetal Toxicity

  • KYPROLIS® can cause fetal harm when administered to a pregnant woman.
  • Advise pregnant women of the potential risk to a fetus. Females of reproductive potential should use effective contraception during treatment with KYPROLIS® and for 6 months following the final dose. Males of reproductive potential should use effective contraception during treatment with KYPROLIS® and for 3 months following the final dose.

Adverse Reactions

  • The most common adverse reactions occurring in at least 20% of patients taking KYPROLIS® in the combination therapy trials: anemia, diarrhea, hypertension, fatigue, upper respiratory tract infection, thrombocytopenia, pyrexia, cough, dyspnea, and insomnia.
  • The most common adverse reactions occurring in at least 20% of patients taking KYPROLIS® in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.

Please see accompanying full Prescribing Information.

INDICATIONS

  • KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone, or with lenalidomide plus dexamethasone, or with daratumumab plus dexamethasone, or with daratumumab plus hyaluronidase-fihj plus dexamethasone, or with isatuximab plus dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
  • KYPROLIS® is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.

IMPORTANT SAFETY INFORMATION FOR KYPROLIS®

Cardiac Toxicities

  • New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS®. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of administration.
  • Monitor patients for signs or symptoms of cardiac failure or ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS® for Grade 3 or 4 cardiac adverse reactions until recovery, and consider whether to restart at 1 dose level reduction based on a benefit/risk assessment.
  • While adequate hydration is required prior to each dose in Cycle 1, monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate.
  • For patients ≥ 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment prior to starting treatment with KYPROLIS® and remain under close follow-up with fluid management.

Acute Renal Failure

  • Cases of acute renal failure, including some fatal renal failure events, and renal insufficiency (including renal failure) have occurred. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS® monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.

Tumor Lysis Syndrome

  • Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred. Patients with a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly, and withhold until resolved.

Pulmonary Toxicity

  • Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue KYPROLIS®.

Pulmonary Hypertension

  • Pulmonary arterial hypertension (PAH) was reported. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS® for PAH until resolved or returned to baseline and consider whether to restart based on a benefit/risk assessment.

Dyspnea

  • Dyspnea was reported in patients treated with KYPROLIS®. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop KYPROLIS® for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart based on a benefit/risk assessment.

Hypertension

  • Hypertension, including hypertensive crisis and hypertensive emergency, has been observed, some fatal. Control hypertension prior to starting KYPROLIS®. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS® and evaluate. Consider whether to restart based on a benefit/risk assessment.

Venous Thrombosis

  • Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed. Provide thromboprophylaxis for patients being treated with the combination of KYPROLIS® with dexamethasone or with lenalidomide plus dexamethasone or with daratumumab and dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.
  • For patients using hormonal contraception associated with a risk of thrombosis, consider an alternative method of effective contraception during treatment.

Infusion-Related Reactions

  • Infusion-related reactions, including life-threatening reactions, have occurred. Signs and symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, laryngeal edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration. Premedicate with dexamethasone to reduce the incidence and severity of infusion-related reactions.

Hemorrhage

  • Fatal or serious cases of hemorrhage have been reported. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate.

Thrombocytopenia

  • KYPROLIS® causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Monitor platelet counts frequently during treatment. Reduce or withhold dose as appropriate.

Hepatic Toxicity and Hepatic Failure

  • Cases of hepatic failure, including fatal cases, have occurred. KYPROLIS® can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate.

Thrombotic Microangiopathy

  • Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome, have occurred. Monitor for signs and symptoms of TTP/HUS. Discontinue if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS® may be restarted. The safety of reinitiating KYPROLIS® is not known.

Posterior Reversible Encephalopathy Syndrome (PRES)

  • Cases of PRES have occurred in patients receiving KYPROLIS®. If PRES is suspected, discontinue and evaluate with appropriate imaging. The safety of reinitiating KYPROLIS® is not known.

Progressive Multifocal Leukoencephalopathy (PML)

  • Cases of PML, including fatal cases, have occurred. In addition to KYPROLIS®, other contributary factors may include prior or concurrent use of immunosuppressive therapy. Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms. If PML is suspected, discontinue and initiate evaluation for PML including neurology consultation.

Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-ineligible Patients

  • In a clinical trial of transplant-ineligible patients with newly diagnosed multiple myeloma comparing KYPROLIS®, melphalan, and prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher incidence of serious and fatal adverse reactions was observed in patients in the KMP arm. KMP is not indicated for transplant-ineligible patients with newly diagnosed multiple myeloma.

Embryo-fetal Toxicity

  • KYPROLIS® can cause fetal harm when administered to a pregnant woman.
  • Advise pregnant women of the potential risk to a fetus. Females of reproductive potential should use effective contraception during treatment with KYPROLIS® and for 6 months following the final dose. Males of reproductive potential should use effective contraception during treatment with KYPROLIS® and for 3 months following the final dose.

Adverse Reactions

  • The most common adverse reactions occurring in at least 20% of patients taking KYPROLIS® in the combination therapy trials: anemia, diarrhea, hypertension, fatigue, upper respiratory tract infection, thrombocytopenia, pyrexia, cough, dyspnea, and insomnia.
  • The most common adverse reactions occurring in at least 20% of patients taking KYPROLIS® in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.

Please see accompanying full Prescribing Information.

INDICATIONS

  • KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone, or with lenalidomide plus dexamethasone, or with daratumumab plus dexamethasone, or with daratumumab plus hyaluronidase-fihj plus dexamethasone, or with isatuximab plus dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
  • KYPROLIS® is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
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References: 1. Dimopoulos MA, Moreau P, Palumbo A, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomized, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17:27-38. 2. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary.