INDICATION
Indications
  • KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone or with lenalidomide plus dexamethasone or with daratumumab and 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 adult patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
  • ... Read More 
FDA APPROVED
KYPROLIS®+Darzalex® (daratumumab)+dexamethasone
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Results by patient type

These data have been compiled to provide an overview of efficacy with respect to one or more characteristics that may apply to this patient type, and certain data may also apply to other patient types represented herein.

These data were compiled from post hoc analyses of the KRd vs Rd and Kd vs Vd studies to provide a categorical overview of efficacy by patient type. The four defined patient types are based on one or more characteristics that may be used to differentiate your patients with relapsed or refractory multiple myeloma.

 

Standard Risk1,2

High Risk1,2

Fit3,4,*

FIT with a
STANDARD RISK

FIT with a
HIGH RISK

Frail3,4,*

FRAIL with a
STANDARD RISK

FRAIL with a
HIGH RISK

FIT with a
STANDARD RISK

FIT with a
HIGH RISK

FRAIL with a
STANDARD RISK

FRAIL with a
HIGH RISK

High Risk1,2

Defined as relapse within 12 months from transplant or progression within the first year of diagnosis, high cytogenetic risk (from FISH) with chromosomal abnormalities (ie, t(4;14), t(14;16), t(14;20), del(17p), 1q gain), R-ISS stage III, high-risk gene expression profiling, and/or high PC S-phase.

Standard Risk1,2

Defined as cytogenetic abnormalities that are not considered high risk (trisomies, t(11;14), t(6;14)), and/or R-ISS stage I.

Fit3,4,*

Defined as a person < 75 years of age, ECOG Performance Status 0-1, no or well-controlled comorbidities, adequate renal and hepatic function, and/or no significant cardiovascular risk factors.

Frail3,4,*

Defined as a person ≥ 75 years of age, ECOG Performance Status of 2 or more, wheelchair bound, having comorbidities (including diabetes or congestive heart failure), renal impairment, and/or hepatic impairment.

KYPROLIS®-based regimens (KRd and Kd) demonstrated superior median progression-free survival vs Rd and Vd, respectively5,†,‡

KRd 27 mg/m2 as a triplet therapy

8.7-month increase in median PFS: 26.3 months (KRd) vs 17.6 months (Rd); hazard ratio (KRd/Rd) = 0.69 (95% CI: 0.57-0.83); two-sided P = 0.00015

Kd 56 mg/m2 as a doublet therapy

9.3-month increase in median PFS: 18.7 months (Kd) vs 9.4 months (Vd); hazard ratio (Kd/Vd) = 0.53 (95% CI: 0.44-0.65); one-sided P < 0.00015

CI = confidence interval; ECOG = Eastern Cooperative Oncology Group; FISH = fluorescence in situ hybridization; IMWG = International Myeloma Working Group; ISS = International Staging System; Kd = KYPROLIS® (carfilzomib) and dexamethasone; KRd = KYPROLIS® (carfilzomib), lenalidomide, and dexamethasone; PC = plasma cell; Rd = lenalidomide and dexamethasone; R-ISS = Revised International Staging System; Vd = VELCADE® (bortezomib) and dexamethasone.

Analyses by patient characteristic: high-risk/fit

High-risk/fit patient description§

  • This is a patient who is likely to have high cytogenetic risk (as determined by FISH sequencing)
  • Additionally, this patient may be young (< 75 years of age), or older with good physical function (ECOG Performance Status 0-1), and normal renal and hepatic function
  • KRd
High-riskEarly relapse during prior therapy< 70 years of agePrior stem cell transplantPrior bortezomib exposure
PFS and ≥ CR6

PFS

High-risk/fit patient (KRd): 9.2-month increase in progression-free survivalHigh-risk/fit patient (KRd): 9.2-month increase in progression-free survival
PFS, ORR, and Rate of ≥ CR7

PFS

High-risk/fit patient with early relapse during prior therapy (KRd): increase of nearly 11 months in progression-free survivalHigh-risk/fit patient with early relapse during prior therapy (KRd): increase of nearly 11 months in progression-free survival
PFS and ORR8

PFS

High-risk/fit patient aged < 70 years (KRd): increase of 11 months in progression-free survivalHigh-risk/fit patient aged < 70 years (KRd): increase of 11 months in progression-free survival
PFS and ORR9

PFS

High-risk/fit patient with prior stem cell transplant (KRd): increase of nearly 9 months in progression-free survivalHigh-risk/fit patient with prior stem cell transplant (KRd): increase of nearly 9 months in progression-free survival
PFS10
High-risk/fit patient with prior bortezomib exposure (KRd): increase of nearly 8 months in progression-free survivalHigh-risk/fit patient with prior bortezomib exposure (KRd): increase of nearly 8 months in progression-free survival

Analyses by patient characteristic: standard-risk/fit

Standard-risk/fit patient description**

  • This is a patient who most likely does not have high cytogenetic risk (determined by FISH) or high tumor burden at the time of relapse
  • Additionally, this patient may be young (< 75 years of age), or older with good physical function (ECOG Performance Status 0-1), ISS I, and normal renal and hepatic function
  • KRd
Standard-risk< 70 years of ageAt first relapsePrior stem cell transplantPrior bortezomib exposure
PFS and ≥ CR6

PFS

Standard-risk/fit patient (KRd): increase of more than 10 months in progression-free survivalStandard-risk/fit patient (KRd): increase of more than 10 months in progression-free survival
PFS and ORR8

PFS

Standard-risk/fit patient aged < 70 years (KRd): increase of 11 months in progression-free survivalStandard-risk/fit patient aged < 70 years (KRd): increase of 11 months in progression-free survival
PFS and ≥ CR10

PFS

Standard-risk/fit patient at first relapse (KRd): increase of 12 months in progression-free survivalStandard-risk/fit patient at first relapse (KRd): increase of 12 months in progression-free survival
PFS and ORR9

PFS

Standard-risk/fit patient with prior stem cell transplant (KRd): increase of nearly 9 months in progression-free survivalStandard-risk/fit patient with prior stem cell transplant (KRd): increase of nearly 9 months in progression-free survival
PFS10
Standard-risk/fit patient with prior bortezomib exposure (KRd): increase of nearly 8 months in progression-free survivalStandard-risk/fit patient with prior bortezomib exposure (KRd): increase of nearly 8 months in progression-free survival

Analyses by patient characteristic: high-risk/frail

High-risk/frail patient description††

  • This is a patient who is likely to have high cytogenetic risk (as determined by FISH sequencing)
  • Additionally, this patient may be older (≥ 75), ECOG of at least 2, R-ISS II or III, renally impaired, hepatically impaired, wheelchair bound, and have comorbidities such as diabetes
  • KRd
  • Kd
High-riskEarly relapse during prior therapy≥ 70 years of agePrior stem cell transplant
PFS and ≥ CR6

PFS

High-risk/frail patient (KRd): 9.2-month increase in progression-free survivalHigh-risk/frail patient (KRd): 9.2-month increase in progression-free survival
PFS, ORR, and ≥ CR7

PFS

High-risk/frail patient with early relapse during prior therapy (KRd): increase of nearly 11 months in progression-free survivalHigh-risk/frail patient with early relapse during prior therapy (KRd): increase of nearly 11 months in progression-free survival
PFS and ORR8

PFS

High-risk/frail patient aged ≥ 70 (KRd): increase of nearly 8 months in progression-free survivalHigh-risk/frail patient aged ≥ 70 (KRd): increase of nearly 8 months in progression-free survival
PFS and ORR9

PFS

High-risk/frail patient with prior stem cell transplant (KRd): increase of nearly 9 months in progression-free survivalHigh-risk/frail patient with prior stem cell transplant (KRd): increase of nearly 9 months in progression-free survival
High-riskEarly relapse during prior therapyRenal function: CrCL ≥ 15 to < 80 mL/minRenal function: CrCL ≥ 80 mL/minAt first relapsePrior stem cell transplantPrior bortezomib exposurePrior lenalidomide exposure< 65 years of age 65-74 years of age≥ 75 years of age
PFS, ORR, and ≥ CR11

PFS

High-risk/frail patient (Kd): increase of nearly 3 months in progression-free survivalHigh-risk/frail patient (Kd): increase of nearly 3 months in progression-free survival
PFS7
High-risk/frail patient with early relapse during prior therapy (Kd): increase of over 8 months in progression-free survivalHigh-risk/frail patient with early relapse during prior therapy (Kd): increase of over 8 months in progression-free survival
PFS, OS, ORR, and ≥ CR12

PFS

High-risk/frail patient with renal function ≥15 to < 50 mL/min (Kd): increase of 8.4 in median PFS; High-risk/frail patient with renal function 50 to < 80 mL/min (Kd): increase of 9.2 in median PFSHigh-risk/frail patient with renal function ≥15 to < 50 mL/min (Kd): increase of 8.4 in median PFS; High-risk/frail patient with renal function 50 to < 80 mL/min (Kd): increase of 9.2 in median PFSHigh-risk/frail patient with renal function &ge;15 to &lt; 50 mL/min (Kd): increase of 16.6 in median OS; High-risk/frail patient with renal function 50 to &lt; 80 mL/min (Kd): median OS was not reachedHigh-risk/frail patient with renal function ≥15 to < 50 mL/min (Kd): increase of 16.6 in median OS; High-risk/frail patient with renal function 50 to < 80 mL/min (Kd): median OS was not reached
PFS, OS, ORR, and ≥ CR12

PFS

High-risk/frail patient with renal function ≥ 80 mL/min (Kd): increase of 5.4 months in median OS. Median PFS was not reachedHigh-risk/frail patient with renal function ≥ 80 mL/min (Kd): increase of 5.4 months in median OS. Median PFS was not reached
PFS and ORR13

PFS

High-risk/frail patient at first relapse (Kd): increase of over 12 months in progression-free survivalHigh-risk/frail patient at first relapse (Kd): increase of over 12 months in progression-free survival
Reduced risk in disease progression or death and ORR9

Reduced risk for progression or death

High-risk/frail patient with prior stem cell transplant (Kd): 39% reduced risk in disease progression or deathHigh-risk/frail patient with prior stem cell transplant (Kd): 39% reduced risk in disease progression or death

(HR = 0.61; 95% CI: 0.47-0.79)
Median PFS has not been reached for Kd vs
10.2 months for Vd

PFS and ORR13

PFS

High-risk/frail patient with prior bortezomib exposure at first relapse (Kd): increase of over 7 months in progression-free survivalHigh-risk/frail patient with prior bortezomib exposure at first relapse (Kd): increase of over 7 months in progression-free survival
PFS and ORR at first relapse13

PFS

High-risk/frail patient with prior lenalidomide exposure at first relapse (Kd): increase of over 5 months in progression-free survivalHigh-risk/frail patient with prior lenalidomide exposure at first relapse (Kd): increase of over 5 months in progression-free survival
PFS, OS, and ORR14,15

PFS

High-risk/frail patient aged < 65 years (Kd): progression-free survivalHigh-risk/frail patient aged < 65 years (Kd): progression-free survival
PFS, OS, and ORR14,15

PFS

High-risk/frail patient aged 65-74 (Kd): increase of over 6 months in progression-free survivalHigh-risk/frail patient aged 65-74 (Kd): increase of over 6 months in progression-free survival
PFS, OS, and ORR14,15

PFS

High-risk/frail patient aged ≥ 75 (Kd): increase of nearly 10 months in progression-free survivalHigh-risk/frail patient aged ≥ 75 (Kd): increase of nearly 10 months in progression-free survival

Analyses by patient characteristic: standard-risk/frail

Standard-risk/frail patient description‡‡

  • This is a patient who most likely does not have high cytogenetic risk (determined by FISH) or high tumor burden at the time of relapse
  • Additionally, this patient may be older (≥ 75), ECOG 2 or more, R-ISS I, renally impaired, hepatically impaired, wheelchair bound, and have comorbidities such as diabetes
  • Kd
Standard-riskAt first relapsePrior bortezomib exposurePrior lenalidomide exposure< 65 years of age65-74 years of age≥ 75 years of age
PFS, ORR, and ≥ CR11

PFS

Standard-risk/frail patient (Kd): progression-free survivalStandard-risk/frail patient (Kd): progression-free survival
PFS and ORR13

PFS

Standard-risk/frail patient at first relapse (Kd): increase of over 12 months in progression-free survivalStandard-risk/frail patient at first relapse (Kd): increase of over 12 months in progression-free survival
PFS and ORR13

PFS

Standard-risk/frail patient with prior bortezomib exposure (Kd): increase of over 7 months in progression-free survivalStandard-risk/frail patient with prior bortezomib exposure (Kd): increase of over 7 months in progression-free survival
PFS and ORR at first relapse13

PFS

Standard-risk/frail patient with prior lenalidomide exposure (Kd): increase of over 5 months in progression-free survivalStandard-risk/frail patient with prior lenalidomide exposure (Kd): increase of over 5 months in progression-free survival
PFS, OS, and ORR14,15

PFS

Standard-risk/frail patient aged < 65 years (Kd): progression-free survivalStandard-risk/frail patient aged < 65 years (Kd): progression-free survival
PFS, OS, and ORR14,15

PFS

Standard-risk/frail patient aged 65-74 years (Kd): increase of over 6 months in progression-free survivalStandard-risk/frail patient aged 65-74 years (Kd): increase of over 6 months in progression-free survival
PFS, OS, and ORR14,15

PFS

Standard-risk/frail patient aged ≥ 75 (Kd): increase of nearly 10 months in progression-free survivalStandard-risk/frail patient aged ≥ 75 (Kd): increase of nearly 10 months in progression-free survival

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 in the combination therapy trials: anemia, diarrhea, fatigue, hypertension, pyrexia, upper respiratory tract infection, thrombocytopenia, cough, dyspnea, and insomnia.
  • The most common adverse reactions 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 and 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 adult 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 in the combination therapy trials: anemia, diarrhea, fatigue, hypertension, pyrexia, upper respiratory tract infection, thrombocytopenia, cough, dyspnea, and insomnia.
  • The most common adverse reactions 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 and 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 adult patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.