ombosis, hypotension
Grade 3 and higher adverse reactions that occurred during Cycles 1–12 with a substantial difference (≥ 2%) between the two arms were neutropenia, thrombocytopenia, hypokalemia, and hypophosphatemia.
Laboratory Abnormalities
Table 9 describes Grade 3–4 laboratory abnormalities reported at a rate of ≥ 10% in the KRd arm for patients who received combination therapy.
Table 9: Grade 3–4 Laboratory Abnormalities (≥ 10% in the KRd Arm) in Cycles 1–12 (20/27 mg/m2 Regimen In Combination with Lenalidomide and Dexamethasone)
KRd = Kyprolis, lenalidomide, and dexamethasone; Rd = lenalidomide and dexamethasone
Safety Experience with Kyprolis in Combination with Dexamethasone in Patients with Multiple Myeloma
The safety of Kyprolis in combination with dexamethasone was eva luated in an open-label, randomized trial of patients with relapsed multiple myeloma. The study treatment is described in Section 14.2. Patients received treatment for a median duration of 40 weeks in the Kyprolis/dexamethasone (Kd) arm and 27 weeks in the bortezomib/dexamethasone (Vd) arm.
Deaths due to adverse reactions within 30 days of last study treatment occurred in 22/463 (5%) patients in the Kd arm and 21/456 (5%) patients in the Vd arm. The causes of death occurring in patients (%) in the two arms (Kd versus Vd) included cardiac 7 (2%) versus 5 (1%), infections 5 (1%) versus 8 (2%), disease progression 6 (1%) versus 4 (1%), pulmonary 3 (1%) versus 2 (< 1%), renal 1 (< 1%) versus 0 (0%), and other adverse events 2 (< 1%) versus 2 (< 1%). Serious adverse reactions were reported in 48% of the patients in the Kd arm and 36% of the patients in the Vd arm. In both treatment arms, pneumonia was the most commonly reported serious adverse reaction (6% versus 9%). Discontinuation due to any adverse reaction occurred in 20% in the Kd arm versus 21% in the Vd arm. The most common reaction leading to discontinuation was cardiac failure in the Kd arm (n = 6, 1.3%) and peripheral neuropathy in the Vd arm (n = 19, 4.2%).
Common Adverse Reactions (≥ 10%)
Adverse reactions in the first 6 months of therapy that occurred at a rate of 10% or greater in the Kd arm are presented in Table 10.
Table 10: Most Common Adverse Reactions (≥ 10% in the Kd Arm) Occurring in Months 1–6 (20/56 mg/m2 Regimen In Combination with Dexamethasone)
Kd = Kyprolis and dexamethasone; Vd = bortezomib and dexamethasone
Thrombocytopenia includes platelet count decreased and thrombocytopenia.
Peripheral neuropathies include peripheral neuropathy, peripheral sensory neuropathy, and peripheral motor neuropathy.
See Clinical Studies (14.2).
Dyspnea includes dyspnea and dyspnea exertional.
Hypertension includes hypertension, hypertensive crisis, and hypertensive emergency.
The event rate of ≥ Grade 2 peripheral neuropathy in the Kd arm was 6% (95% CI: 4, 8) versus 32% (95% CI: 28, 36) in the Vd arm.
Adverse Reactions Occurring at a Frequency of < 10%
Blood and lymphatic system disorders: febrile neutropenia, leukopenia, lymphopenia, neutropenia, thrombotic microangiopathy, thrombotic thrombocytopenic purpura
Cardiac disorders: atrial fibrillation, cardiac arrest, cardiac failure, cardiac failure congestive, myocardial infarction, myocardial ischemia, palpitations, tachycardia
Eye disorders: cataract, vision blurred
Gastrointestinal disorders: abdominal pain, abdominal pain upper, dyspepsia, toothache
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