KYPROLIS (carfilzomib) for Injection Menu
Kd vs Vd STUDY

Kd safety profile

Treatment duration

Median treatment duration was 40 weeks with Kd vs 27 weeks with Vd1-3

Median duration of treatment with Kd vs Vd
See median duration of treatment in the Kd vs Vd study

Safety experience with Kd vs Vd1,2

Kd (n = 463) Vd (n = 456)
Deaths due to ADRs within 30 days of last therapy dose 5% 5%
Discontinuation of at least one drug in the regimen due to ADRs 20% 21%
  • Causes of death (Kd vs Vd patients)1:
    • cardiac, 7 (2%) vs 5 (1%)
    • infections, 5 (1%) vs 8 (2%)
    • disease progression, 6 (1%) vs 4 (1%)
    • pulmonary, 3 (1%) vs 2 (< 1%)
    • renal, 1 (< 1%) vs 0 (0%)
    • other adverse reactions, 2 (< 1%) vs 2 (< 1%)
  • Most common reaction leading to discontinuation: cardiac failure for Kd (n = 6, 1.3%) and peripheral neuropathy for Vd (n = 19, 4.2%)1
  • Serious adverse reactions: 48% for Kd and 36% for Vd1
  • Pneumonia was the most commonly reported serious adverse reaction, with 6% in the Kd arm and 9% in the Vd arm1
  • Discontinuation due to disease progression: 25% for Kd vs 36% for Vd2
  • Dose reductions due to ADRs: 23% for Kd vs 48% for Vd2

Kd = KYPROLIS® and dexamethasone; Vd = VELCADE® (bortezomib) and dexamethasone; ADR = adverse reaction.

Adverse reactions

Most common adverse reactions (≥ 10% in the Kd Arm) occurring in months 1-61

Adverse reactions by body system Kd (n = 463), % Vd (n = 456), %
Any Grade Grade ≥ 3 Any Grade Grade ≥ 3
Blood and lymphatic system disorders
Anemia 35 12 25 9
Thrombocytopenia* 27 10 25 14
Gastrointestinal disorders
Diarrhea 24 3 33 6
Nausea 15 1 15 1
Constipation 13 0 24 1
Vomiting 10 1 7 1
General disorders and administration site conditions
Fatigue 24 3 27 6
Pyrexia 22 2 11 1
Edema peripheral 16 1 16 1
Asthenia 15 2 14 3
Infections and infestations
Upper respiratory tract infection 14 1 12 1
Bronchitis 12 1 6 0
Nasopharyngitis 10 0 9 0
Musculoskeletal and connective tissue disorders
Muscle spasms 14 0 5 1
Back pain 13 2 13 2
Nervous system disorders
Headache 15 1 8 0
Peripheral neuropathies 12 2 37 5
Psychiatric disorders
Insomnia 22 1 25 2
Respiratory, thoracic, and mediastinal disorders
Dyspnea 27 5 15 2
Cough§ 20 0 13 0
Vascular disorders
Hypertension** 17 6 7 3
* Thrombocytopenia includes platelet count decreased and thrombocytopenia.
Peripheral neuropathies include peripheral neuropathy, peripheral sensory neuropathy, and peripheral motor neuropathy.
Dyspnea includes dyspnea and dyspnea exertional.
§ Cough includes cough and productive cough.
** Hypertension includes hypertension, hypertensive crisis, and hypertensive emergency.
  • The most common treatment-emergent adverse reactions observed in KYPROLIS® patients were predominantly Grades 1-21

Adverse reactions of interest1,2

Kd (n = 463) Vd (n = 456)
Preferred term (%) All grades Grade ≥ 3 All grades Grade ≥ 3
Acute renal failure†† 8 4 5 3
Cardiac failure‡‡ 8 5 3 2
Ischemic heart disease§§ 3 2 2 2
Peripheral neuropathy*** 19 2 52 8
Pulmonary hypertension††† 1 1 0.2 0.2
†† Acute renal failure included (in descending order of frequency): acute renal failure, renal failure, renal impairment, acute prerenal failure, anuria, oliguria, and prerenal failure.
‡‡ Cardiac failure included (in descending order of frequency): cardiac failure, ejection fraction decreased, pulmonary edema, acute cardiac failure, congestive cardiac failure, acute pulmonary edema, acute left ventricular failure, chronic cardiac failure, cardiopulmonary failure, hepatojugular reflux, right ventricular failure, and left ventricular failure.
§§ Ischemic heart disease included (in descending order of frequency): angina pectoris, acute coronary syndrome, myocardial infarction, increased troponin T, coronary artery disease, increased troponin I, acute myocardial infarction, myocardial ischemia, and cardiomyopathy stress.
*** Peripheral neuropathy included (in descending order of frequency): peripheral neuropathy, peripheral sensory neuropathy, neuralgia, decreased vibratory sense, polyneuropathy, sensory loss, amyotrophy, peripheral motor neuropathy, peripheral sensorimotor neuropathy, sensory disturbance, and toxic neuropathy.
††† Pulmonary hypertension included (in decreasing order of frequency): pulmonary hypertension, right ventricular failure, and pulmonary arterial hypertension.
  • ≥ Grade 2 peripheral neuropathy: 6% in the Kd arm (95% CI: 4, 8) vs 32% in the Vd arm (95% CI: 28, 36)1
  • Among patients in the Vd group, 82% received subcutaneous VELCADE® (bortezomib) throughout their treatment1

References

1. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 2. 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(1):27-38. 3. Data on file (ENDEAVOR CSR), Amgen, Inc., 2015. 1. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 2. 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(1):27-38. 3. Data on file (ENDEAVOR CSR), Amgen, Inc., 2015.

Important Safety Information

Cardiac Toxicities

  • New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive 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 KYPROLIS administration.
  • Monitor patients for clinical signs or symptoms of cardiac failure or cardiac ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart KYPROLIS 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 in patients with baseline cardiac failure or who are at risk for cardiac failure.
  • 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 (including blood pressure and fluid management) prior to starting treatment with KYPROLIS and remain under close follow-up.

Acute Renal Failure

Tumor Lysis Syndrome

Pulmonary Toxicity

Pulmonary Hypertension

Dyspnea

Hypertension

Venous Thrombosis

Infusion Reactions

Hemorrhage

Thrombocytopenia

Hepatic Toxicity and Hepatic Failure

Thrombotic Microangiopathy

Posterior Reversible Encephalopathy Syndrome (PRES)

Embryo-fetal Toxicity

Adverse reactions

Please see full Prescribing Information.

Indications