Nasopharyngitis 63 (16) 0 43 (11) 0
Bronchitis 54 (14) 5 (1) 39 (10) 2 (1)
Pneumonia a 54 (14) 35 (9) 43 (11) 27 (7)
Hypokalemia 78 (20) 22 (6) 35 (9) 12 (3)
Hypocalcemia 55 (14) 10 (3) 39 (10) 5 (1)
Hyperglycemia 43 (11) 18 (5) 33 (9) 15 (4)
Metabolism and Nutrition Disorders
Musculoskeletal and Connective Tissue Disorders
Muscle spasms
88 (22) 3 (1) 73 (19) 3 (1)
43 (11) 7 (2) 37 (10) 4 (1)
63 (16) 6 (2) 50 (13) 8 (2)
91 (23) 2 (1) 52 (13) 0
70 (18) 9 (2) 58 (15) 6 (2)
45 (12) 5 (1) 53 (14) 5 (1)
Embolic and thrombotic events venous e 49 (13) 16 (4) 22 (6) 9 (2)
Hypertension f 41 (11) 12 (3) 15 (4) 4 (1)
Nervous System Disorders
Peripheral neuropathies b
Psychiatric Disorders
Insomnia
Respiratory, Thoracic, and Mediastinal Disorders
Cough c
Dyspnea
d
Skin and Subcutaneous Tissue Disorders
Rash
Vascular Disorders
KRd = Kyprolis, lenalidomide, and dexamethasone; Rd = lenalidomide and dexamethasone.
a
Pneumonia includes pneumonia and bronchopneumonia.
b
Peripheral neuropathies includes peripheral neuropathy, peripheral sensory neuropathy, and peripheral
motor neuropathy.
c
Cough includes cough and productive cough.
d
Dyspnea includes dyspnea and dyspnea exertional.
e
Embolic and thrombotic events, venous include deep vein thrombosis, pulmonary embolism,
thrombophlebitis superficial, thrombophlebitis, venous thrombosis limb, post thrombotic syndrome,
venous thrombosis.
f
Hypertension includes hypertension, hypertensive crisis.
There were 274 (70%) patients in the KRd arm who received treatment beyond Cycle 12. There were no new
clinically relevant adverse reactions that emerged in the later treatment cycles.
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.
Safety Experience with Kyprolis in Combination with Dexamethasone in Patients with Multiple Myeloma
The safety of Kyprolis in combination with dexamethasone was evaluated in an open-label, randomized trial
of patients with relapsed multiple myeloma. 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 vs. 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% vs. 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%).
Most Common Adverse Reactions (≥ 10% in the Kd Arm) Occurring in Months 1–6 (20/56 mg/m 2
Regimen in Combination with Dexamethasone)
Kd
(N = 463), n (%)
Adverse Reaction by Body System
Vd
(N = 456), n (%)
Any Grade ≥ Grade 3 Any Grade
≥ Grade 3
Anemia 160 (35) 57 (12) 112 (25) 43 (9)
Thrombocytopenia a 127 (27) 46 (10) 112 (25) 65 (14)
Diarrhea 111 (24) 14 (3) 150 (33) 26 (6)
Nausea 69 (15) 4 (1) 66 (15) 3 (1)
Constipation 58 (13) 1 (0) 109 (24) 6 (1)
Vomiting 45 (10) 5 (1) 32 (7) 3 (1)
Blood and Lymphatic System Disorders
Gastrointestinal Disorders
General Disorders and Administration Site Conditions
Fatigue 112 (24) 13 (3) 124 (27) 25 (6)
Pyrexia 102 (22) 9 (2) 52 (11) 3 (1)
Peripheral edema 75 (16) 3 (1) 73 (16) 3 (1)
Asthenia 71 (15) 9 (2) 66 (14) 13 (3)
Upper respiratory tract infection 66 (14) 4 (1) 54 (12) 3 (1)
Bronchitis 54 (12) 5 (1) 26 (6) 2 (0)
Nasopharyngitis 45 (10) 0 (0) 42 (9) 1 (0)
Infections and Infestations
Musculoskeletal and Connective Tissue Disorders
Muscle spasms 66 (14) 1 (0) 22 (5) 3 (1)
Back pain 58 (13) 7 (2) 60 (13) 8 (2)
Headache 68 (15) 4 (1) 38 (8) 2 (0)
Peripheral neuropathies b 54 (12) 7 (2) 167 (37) 23 (5)
Nervous System Disorders
Psychiatric Disorders
Insomnia
103 (22)
5 (1) 113 (25) 10 (2)
Respiratory, Thoracic, and Mediastinal Disorders
Dyspnea c 123 (27) 23 (5) 66 (15) 8 (2)
Cough 91 (20) 0 (0) 61 (13) 2 (0)
80 (17) 29 (6) 33 (7) 12 (3)
d
Vascular Disorders
Hypertension e
Kd = Kyprolis and dexamethasone; Vd = bortezomib and dexamethasone.
a
Thrombocytopenia includes platelet count decreased and thrombocytopenia.
b
Peripheral neuropathies include peripheral neuropathy, peripheral sensory neuropathy, and peripheral
motor neuropathy.
c
Dyspnea includes dyspnea and dyspnea exertional.
d
Cough includes cough and productive cough.
e
Hypertension includes hypertension, hyperten