eral disorders and administration site conditions: chest pain, chills, infusion site reactions (including inflammation, pain, and erythema), pain
Hepatobiliary disorders: cholestasis, hepatic failure, hyperbilirubinemia
Immune system disorders: drug hypersensitivity
Infections and infestations: bronchopneumonia, influenza, pneumonia, sepsis, urinary tract infection, viral infection
Metabolism and nutrition disorders: decreased appetite, dehydration, hypercalcemia, hyperkalemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, tumor lysis syndrome
Musculoskeletal and connective tissue disorders: muscular weakness, musculoskeletal chest pain, musculoskeletal pain, myalgia
Nervous system disorders: cerebrovascular accident, dizziness, hypoesthesia, paresthesia, posterior reversible encephalopathy syndrome
Psychiatric disorders: anxiety
Renal and urinary disorders: renal failure, renal failure acute, renal impairment
Respiratory, thoracic and mediastinal disorders: acute respiratory distress syndrome, dysphonia, epistaxis, interstitial lung disease, oropharyngeal pain, pneumonitis pulmonary embolism, pulmonary edema, pulmonary hypertension, wheezing
Skin and subcutaneous tissue disorders: erythema, hyperhidrosis, pruritus, rash
Vascular disorders: deep vein thrombosis, flushing, hypotension
Laboratory Abnormalities
Table 11 describes Grades 3–4 laboratory abnormalities reported at a rate of ≥ 10% in the Kd arm.
Table 11: Grades 3–4 Laboratory Abnormalities (≥ 10%) in Months 1–6 (20/56 mg/m2 Regimen In Combination with Dexamethasone)
Kd = Kyprolis and dexamethasone; Vd = bortezomib and dexamethasone
Calculated using the Cockcroft-Gault formula
Safety Experience with Kyprolis in Patients with Multiple Myeloma who Received Monotherapy
The safety of Kyprolis, dosed at 20/27 mg/m2 by up to 10-minute infusion, was eva luated in clinical trials in which 598 patients with relapsed and/or refractory myeloma received Kyprolis monotherapy starting with the 20 mg/m2 dose in Cycle 1, Day 1 and escalating to 27 mg/m2 on Cycle 1, Day 8 or Cycle 2, Day 1. Premedication with dexamethasone 4 mg was required before each dose in Cycle 1 and was optional for subsequent cycles. The median age was 64 years (range 32–87), and approximately 57% were male. The patients received a median of 5 (range 1–20) prior regimens. The median number of cycles initiated was 4 (range 1–35).
Serious adverse reactions, regardless of causality, were reported in 50% of patients in the pooled Kyprolis monotherapy studies (N = 598). The most common serious adverse reactions were: pneumonia (8%), acute renal failure (5%), disease progression (4%), pyrexia (3%), hypercalcemia (3%), congestive heart failure (3%), multiple myeloma (3%), anemia (2%), and dyspnea (2%). In patients treated with Kyprolis, the incidence of serious adverse reactions was higher in those ≥ 65 years old and those ≥ 75 years old [see Geriatric Use (8.5)].
Deaths due to adverse reactions within 30 days of the last dose of Kyprolis occurred in 30/598 (5%) patients receiving Kyprolis monotherapy. These adverse reactions were related to cardiac disorders in 10 (2%) patients, infections in 8 (1%) patients, renal disorders in 4 (< 1%) patients, and other adverse reactions in 8 (1%) patients. In a randomized trial comparing Kyprolis as a single age |
