INDICATION
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.
    • ... Read More 
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 KYPROLIS®+Darzalex® (daratumumab)+dexamethasone
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Kd vs Vd study results

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Median PFSPFS at 12 monthsPFS at 24 monthsPFS by 1 previous linePFS by 2 or 3 previous linesPFS by prior bortezomib exposurePFS by bortezomib naivePFS in frail-subgroup patients

Superior median progression-free survival: 18.7 months for Kd vs 9.4 months for Vd1

Kd 56 mg/m2 significantly increased median PFS by 9.3 months vs Vd1

Primary endpoint: PFS1
9.3-month increase in median progression-free survival demonstrated with KYPROLIS#[sup ®] regimen vs VELCADE#[sup ®] regimen (Kd vs Vd)9.3-month increase in median progression-free survival demonstrated with KYPROLIS® regimen vs VELCADE#[sup ®] regimen (Kd vs Vd)
Median PFS

Kd = 18.7 months
Vd = 9.4 months
HR = 0.53 (95% CI: 0.44-0.65);
P < 0.0001, one-sided

Kd: National Comprehensive Cancer Network® (NCCN®) recommended NCCN Clinical Practice Guidelines for Oncology (NCCN Guidelines®)2:

Carfilzomib (KYPROLIS®) in combination with dexamethasone (Kd twice weekly) is included under "recommended regimens" as a treatment option for previously-treated multiple myeloma.2

Carfilzomib (KYPROLIS®) in combination with dexamethasone (Kd twice weekly) has a category 1 designation in the NCCN Guidelines® for Multiple Myeloma (Version 2.2021) for previously treated multiple myeloma.2

NCCN makes no warranties of any kind whatsoever regarding this content, use or application and disclaims any responsibility for their application or use in any way.

DKd = KYPROLIS®+Darzalex® (daratumumab) and dexamethasone; Kd = KYPROLIS®+dexamethasone; PFS = progression-free survival; HR = hazard ratio; CI = confidence interval.

Post hoc analysis: progression-free survival at 12 months: 62.7% with Kd vs 41.5% with Vd3

Progression-free survival at 12 months1,3
Post hoc analysis: Progression-free survival at 12 months with KYPROLIS® regimen was 62.7% vs 41.5% with VELCADE® regimen (Kd vs Vd)Post hoc analysis: Progression-free survival at 12 months with KYPROLIS® regimen was 62.7% vs 41.5% with VELCADE® regimen (Kd vs Vd)

Post hoc analysis: demonstration of progression-free survival at 12 months was not a study objective.

Kd = KYPROLIS® (carfilzomib) and dexamethasone; PFS = progression-free survival; Vd = VELCADE® (bortezomib) and dexamethasone.

Post hoc analysis: progression-free survival at 24 months: 43.9% with Kd vs 22.2% with Vd3

Progression-free survival at 24 months1,3
Post hoc analysis: Progression-free survival at 24 months was 43.9% with KYPROLIS® regimen vs 22.2% with VELCADE® regimen (Kd vs Vd)Post hoc analysis: Progression-free survival at 24 months was 43.9% with KYPROLIS® regimen vs 22.2% with VELCADE® regimen (Kd vs Vd)

At 2 years, nearly twice as many patients were alive without disease progression in the Kd arm vs the Vd arm3

Post hoc analysis: demonstration of progression-free survival at 24 months was not a study objective.

Kd = KYPROLIS® (carfilzomib) and dexamethasone; PFS = progression-free survival; Vd = VELCADE® (bortezomib) and dexamethasone.

Exploratory analysis: At first relapse, Kd demonstrated a 12.1-month increase in median progression-free survival over Vd4

1 previous line of therapy4
Exploratory analysis: At first relapse, Kd demonstrated a 12.1-month improvement in median progression-free survival over VdExploratory analysis: At first relapse, Kd demonstrated a 12.1-month improvement in median progression-free survival over Vd

HR (Kd/Vd) = 0.45 (95% CI: 0.33-0.61)

Although this subgroup analysis was preplanned, demonstration of progression-free survival within these subgroups was not a study objective. The study was not powered to evaluate progression-free survival within each of these subgroups.

CI = confidence interval; HR = hazard ratio; Kd = KYPROLIS® (carfilzomib) and dexamethasone; PFS = progression-free survival; Vd = VELCADE® (bortezomib) and dexamethasone.

Exploratory analysis: Kd demonstrated a 6.5-month increase in median progression-free survival over Vd in patients who had received 2 or 3 previous lines of therapy4

2 or 3 previous lines of therapy4
Exploratory analysis: Kd demonstrated a 6.5-month improvement in median progression-free survival over Vd in patients who had received 2 or 3 previous lines of therapyExploratory analysis: Kd demonstrated a 6.5-month improvement in median progression-free survival over Vd in patients who had received 2 or 3 previous lines of therapy

HR (Kd/Vd) = 0.60 (95% CI: 0.47-0.78)

Although this subgroup analysis was preplanned, demonstration of progression-free survival within these subgroups was not a study objective. The study was not powered to evaluate progression-free survival within each of these subgroups.

CI = confidence interval; HR = hazard ratio; Kd = KYPROLIS® (carfilzomib) and dexamethasone; PFS = progression-free survival; Vd = VELCADE® (bortezomib) and dexamethasone.

Kd progression-free survival results were consistent, independent of prior proteasome inhibitor exposure5

In an exploratory subgroup analysis of patients with prior exposure to bortezomib, results were consistent with overall PFS results5,*

Prior bortezomib exposure5
Exploratory analysis: Kd progression-free survival results were consistent, independent of prior proteasome inhibitor exposureExploratory analysis: Kd progression-free survival results were consistent, independent of prior proteasome inhibitor exposure

HR (Kd/Vd) = 0.56 (95% CI: 0.44-0.73)

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

CI = confidence interval; HR = hazard ratio; Kd = KYPROLIS® (carfilzomib) and dexamethasone; PFS = progression-free survival; Vd = VELCADE® (bortezomib) and dexamethasone.

Kd progression-free survival results were consistent, independent of prior proteasome inhibitor exposure5,*

Bortezomib naive5
Exploratory analysis: Kd progression-free survival results were consistent, independent of prior proteasome inhibitor exposureExploratory analysis: Kd progression-free survival results were consistent, independent of prior proteasome inhibitor exposure

HR (Kd/Vd) = 0.48 (95% CI: 0.36-0.66)

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

CI = confidence interval; HR = hazard ratio; Kd = KYPROLIS® (carfilzomib) and dexamethasone; PFS = progression-free survival; Vd = VELCADE® (bortezomib) and dexamethasone.

Post-hoc analysis: Frail-subgroup patients with Kd 56 mg/m2 experienced mPFS of 18.7 months vs 6.6 months with Vd7,*,†

Patients’ age, ECOG PS, and medical history (comorbidities) were used to evaluate frailty status7,*

Median PFS

*Patients who scored ≥ 2 by the proxy algorithm were categorized as frail-subgroup patients. Scores were calculated by assigning values of 0-2 associated with patient characteristics such as patient age, Charlson Comorbidity Index (CCI), and ECOG PS number. Frail-subgroup patients represented 36% (168/464) and 35% (162/465) of patients in the Kd and Vd arms, respectively.7

Post hoc design

Post hoc analysis: Demonstration of PFS by frailty status was not a study objective. This study was not powered to evaluate PFS efficacy within this subgroup.

†Overall median follow-up for patients in the Kd vs Vd study was approximately 37 months.1

Kd = KYPROLIS®+dexamethasone; mPFS = median progression-free survival; Vd = Velcade® (bortezomib)+dexamethasone; ECOG PS = Eastern Cooperative Oncology Group Performance Status.

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Kd 56 mg/m2 significantly increased median overall survival by 7.6 months vs Vd (Kd 47.6 months vs Vd 40.0 months)1

Kd reduced the risk of death by 21% compared to Vd1

Secondary endpoint: overall survival1
Kd significantly increased median overall survival by 7.6 months vs Vd Kd significantly increased median overall survival by 7.6 months vs Vd
Median OS

Kd = 47.6 months
Vd = 40.0 months
HR (Kd/Vd) = 0.79 (95% CI: 0.65-0.96);
P = 0.01, one-sided

Kd = KYPROLIS®+dexamethasone; Vd = VELCADE® (bortezomib) and dexamethasone; OS = overall survival; HR = hazard ratio; CI = confidence interval.

Response by category≥ CR over time

Kd 56 mg/m2 doubled patients' chance of achieving a complete response or better (Kd vs Vd)1

Secondary endpoint: responses by category1
Kd doubled the patient’s chance of achieving a complete response or better (Kd vs Vd)Kd doubled the patient’s chance of achieving a complete response or better (Kd vs Vd)
  • Post hoc analysis: rates of CR or better in the Kd vs Vd study were consistent regardless of number of prior lines of therapy (1 prior line: 12% Kd vs 8% Vd compared with 2 or 3 prior lines: 13% Kd vs 5% Vd)4
  • Demonstration of CR by line of therapy was not a study objective
IMWG uniform response criteria8
Response Multiple myeloma response criteria
Stringent complete response (sCR) CR as defined below plus normal free light chain (FLC) ratio* and absence of clonal cells in bone marrow biopsy by immunohistochemistry†
Complete response (CR) Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates
Very good partial response (VGPR) Serum and urine M‑protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M‑protein plus urine M‑protein level < 100 mg/24 hours
Partial response (PR)

≥ 50% reduction of serum M‑protein and reduction in 24‑hour urinary M‑protein by ≥ 90% or to < 200 mg/24 hours

If the serum and urine M‑protein are unmeasurable, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M‑protein criteria

If serum and urine M‑protein are unmeasurable, and serum free light assay is also unmeasurable, ≥ 50% reduction in plasma cells is required in place of M‑protein, provided baseline bone marrow plasma cell percentage was ≥ 30%. In addition to these criteria, if present at baseline, a ≥ 50% reduction in the size (SPD)‡ of soft tissue plasmacytomas is also required

Adapted by permission from Elsevier Limited: Lancet Oncol. 2016;17:e328-e346. © 2016.

*All recommendations regarding clinical uses relating to serum FLC levels or FLC ratio are based on results obtained with the validated Freelite test (Binding Site, Birmingham, UK).

†Presence/absence of clonal cells on immunohistochemistry is based upon the kappa/lambda ratio. An abnormal kappa/lambda ratio by immunohistochemistry requires a minimum of 100 plasma cells for analysis. An abnormal ratio reflecting presence of an abnormal clone is kappa/lambda of > 4:1 or < 1:2.

‡Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or MRI scans, or dedicated CT scans where applicable. For patients with only skin involvement, skin lesions should be measured with a ruler. Measurement of tumor size will be determined by the SPD.

Kd = KYPROLIS®+dexamethasone; Vd = Velcade® (bortezomib)+dexamethasone; ≥ CR = complete response or better; ≥ VGPR = very good partial response or better; ORR = overall response rate (CR or better + VGPR + PR); ≥ PR = partial response; IMWG = International Myeloma Working Group; M-protein = monoclonal protein; SPD = sum of the products of the maximal perpendicular diameters of measured lesions; CT = computed tomography; PET = positron-emission tomography; MRI = magnetic resonance imaging.

Post hoc analysis: the longer patients stayed on treatment, the better their chances of reaching ≥ CR6

Cumulative rates of ≥ CR6
Post hoc analysis: the longer patients stayed on treatment, the better their chances of reaching complete response (CR) or betterPost hoc analysis: the longer patients stayed on treatment, the better their chances of reaching complete response (CR) or better
  • Adding KYPROLIS® to dexamethasone doubled the patient's chance of achieving CR or better vs Vd1
  • Post hoc analysis: demonstration of complete response over time was not a study objective

≥ CR = complete response or better; Kd = KYPROLIS® (carfilzomib) and dexamethasone; Vd = bortezomib and dexamethasone.

​

Dr. Richter expert video

See why multiple myeloma specialist Dr. Joshua Richter chooses Kd for his patients with relapsed multiple myeloma

Multiple myeloma specialist Dr. Joshua Richter expert video

Kd = KYPROLIS®+dexamethasone.

​
dosing_icon-svg

See Kd 56 mg/m2  twice-weekly dosing

Kd twice weekly dosing

Next Results by patient type

Results by patient type

Kd 56 mg/m2 vs Vd phase 3 design: N = 929, randomized (1:1), open-label superiority study comparing Kd to Vd in relapsed or refractory multiple myeloma patients who had received 1 to 3 lines of therapy. The primary endpoint was PFS. Select secondary endpoints included OS, overall response rate, duration of response, and safety.1,5

REFERENCES

1. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V2.2021. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed October 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. 3. Data on file, Amgen; 2015. 4. Moreau P, Joshua D, Chng W-J, et al. Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3 ENDEAVOR study. Leukemia. 2017;31:115-122. 5. 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 randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17:27-38. 6. Data on file, Amgen; 2017. 7. Facon T, Niesvizky R, Weisel K, et al. Carfilzomib in relapsed or refractory multiple myeloma: frailty subgroup analysis from phase 3 ASPIRE and ENDEAVOR. Poster presented at: 17th International Myeloma Workshop; September 12-15, 2019; Boston, MA. 8. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17:e328-e346. 9. Dimopoulos MA, Goldschmidt H, Niesvizky R, et al. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18:1327-1337.

All trademarks are the property of their respective owners.

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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.