KYPROLIS (carfilzomib) for Injection Menu

KRd safety profile

Treatment duration

Median number of cycles initiated was 22 cycles (88 weeks) with KRd vs 14 cycles (57 weeks) with Rd1,2

Median duration of treatment with KRd
See median duration of treatment in the KRd vs Rd study

KYPROLIS® was discontinued after 18 cycles in the KRd arm.

Safety experience with KRd vs Rd1,2

KRd (n = 392) Rd (n = 389)
Deaths due to ADRs within 30 days of last therapy dose 7% 7%
Discontinuation of at least one drug in the regimen due to ADRs 26% 25%
  • Most common causes of death (KRd vs Rd patients)1:
    • cardiac, 10 (3%) vs 7 (2%)
    • infection, 9 (2%) vs 10 (3%)
    • renal, 0 (0%) vs 1 (< 1%)
    • other adverse reactions, 9 (2%) vs 10 (3%)
  • Adverse reactions leading to discontinuation of KYPROLIS® occurred in 12% of patients and the most common reactions included pneumonia (1%), myocardial infarction (0.8%), and upper respiratory tract infection (0.8%)1
  • Serious adverse reactions: 60% for KRd vs 54% for Rd1
  • Most common serious adverse reactions (KRd vs Rd)1:
    • pneumonia (14% vs 11%)
    • respiratory tract infection (4% vs 1.5%)
    • pyrexia (4% vs 2%)
    • pulmonary embolism (3% vs 2%)
  • Discontinuation due to disease progression: 40% for KRd vs 50% for Rd2
  • Dose reductions due to ADRs2:
    • KRd arm: KYPROLIS® dose was reduced in 11% of patients, and the lenalidomide dose was reduced in 43% of patients
    • Rd arm: lenalidomide dose was reduced in 39% of patients
Adverse reactions

Most common adverse reactions (≥ 10% in KRd) occurring in Cycles 1-121

Adverse reactions by body system KRd Arm
(n = 392)
Rd Arm
(n = 389)
Any Grade
(%)
≥ Grade 3
(%)
Any Grade
(%)
≥ Grade 3
(%)
Blood and lymphatic system disorders
Anemia 35 14 33 12
Neutropenia 32 27 30 23
Thrombocytopenia 26 15 19 10
Gastrointestinal disorders
Diarrhea 29 2 27 3
Constipation 17 0 14 0
Nausea 15 0 10 1
General disorders and administration site conditions
Fatigue 28 5 27 5
Pyrexia 24 1 17 0
Edema peripheral 16 1 15 1
Asthenia 14 3 12 2
Infections and infestations
Upper respiratory tract infection 22 2 13 1
Nasopharyngitis 16 0 11 0
Bronchitis 14 1 10 1
Pneumonia* 14 9 11 7
Metabolism and nutrition disorders
Hypokalemia 20 6 9 3
Hypocalcemia 14 3 10 1
Hyperglycemia 11 5 9 4
Musculoskeletal and connective tissue disorders
Muscle Spasms 22 1 19 1
Nervous system disorders
Peripheral neuropathies 11 2 10 1
Psychiatric disorders
Insomnia 16 2 13 2
Respiratory, thoracic, and mediastinal disorders
Cough 23 1 13 0
Dyspnea§ 18 2 15 2
Skin and subcutaneous tissue disorders
Rash 12 1 14 1
Vascular disorders
Embolic and thrombotic events, venous** 13 4 6 2
Hypertension†† 11 3 4 1
* Pneumonia includes pneumonia and bronchopneumonia.
Peripheral neuropathies include peripheral neuropathy, peripheral sensory neuropathy, and peripheral motor neuropathy.
Cough includes cough and productive cough.
§ Dyspnea includes dyspnea and dyspnea exertional.
** Embolic and thrombotic events, venous include deep vein thrombosis, pulmonary embolism, thrombophlebitis superficial, thrombophlebitis, venous thrombosis limb, post thrombotic syndrome, venous thrombosis.
†† Hypertension includes hypertension, hypertensive crisis.

References

1. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 2. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142-152. 1. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 2. Orlowski RZ, Kuhn DJ. Proteasome inhibitors in cancer therapy: lessons from the first decade. Clin Cancer Res. 2008;14:1649-1657. 3. Demo SD, Kirk CJ, Aujay MA, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 2007;67:6383-6391. 4. Kuhn DJ, Chen Q, Voorhees PM, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007;110:3281-3290.

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