KYPROLIS (carfilzomib) for Injection Menu
Kd vs Vd study design

Head-to-head superiority study of Kd vs Vd

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

Overview

A phase 3, randomized, open-label, multicenter, superiority study1,2

  • Compared KYPROLIS® plus dexamethasone (Kd) to VELCADE® plus dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma who had received 1 to 3 lines of therapy1
View the Kd vs Vd study design
  • Patients were stratified according to1:
    • Prior proteasome inhibitor therapy (either KYPROLIS® or VELCADE®, or no prior therapy)
    • Lines of prior therapy (1 or 2-3)
    • ISS stage (1 or 2-3)
    • Routes of VELCADE® administration (intravenous or subcutaneous)
  • Primary endpoint was progression-free survival (PFS)1,2
  • Select secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DoR), and safety1,2

ISS = International Staging System.

Baseline characteristics

Baseline characteristics were well-balanced between study arms1,2

Patient demographics and baseline characteristics
Kd (n = 464) Vd (n = 465)
Age, years
Median (range) 65 (35, 89) 65 (30, 88)
≥ 75 years, n (%) 77 (17) 66 (14)
ECOG performance status, n (%)
0 221 (48) 232 (50)
1 211 (46) 203 (44)
2 32 (7) 30 (6)
ISS stage, n (%)
I 212 (46) 205 (44)
II 138 (30) 151 (33)
III 114 (25) 109 (23)
Cytogenetic risk category by FISH, n (%)
High 97 (21) 113 (24)
Standard 284 (61) 291 (63)
Unknown 83 (18) 61 (13)
Creatinine clearance, n (%)
< 30 mL/min 28 (6) 28 (6)
30 to < 50 mL/min 57 (12) 71 (15)
50 to < 80 mL/min 186 (40) 177 (38)
≥ 80 mL/min, n (%) 193 (42) 189 (41)
Baseline neuropathy, n (%)
Grade 1 133 (29) 159 (34)
Grade 2 10 (2) 10 (2)
Prior therapies at baseline
Kd (n = 464) Vd (n = 465)
Number of prior regimens, median (range) 2 (1-3) 2 (1-3)
Prior regimens, n (%)
1 232 (50) 232 (50)
2 157 (34) 145 (31)
3 75 (16) 87 (19)
Prior therapies, n (%)
VELCADE®
250 (54) 252 (54)
Lenalidomide 177 (38) 177 (38)
Thalidomide 211 (46) 247 (53)
Stem cell transplant 266 (57) 272 (59)
Refractory to last prior therapy§ 184 (40) 188 (40)

ECOG = Eastern Cooperative Oncology Group; ISS = International Staging System; FISH = fluorescence in situ hybridization.

Missing FISH data are included with the unknown risk (Kd=28 [6.0%], Vd=31 [6.7%])

One patient in the Vd arm had 4 prior regimens

§Refractory was defined as disease not achieving a minimal response or better, progressing during therapy, or within 60 days after completion of therapy

Note: Carfilzomib (KYPROLIS®) in combination with dexamethasone (Kd) has a category 1 designation in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma (Version 3.2017) for previously treated multiple myeloma.3

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. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.3.2017. © National Comprehensive Cancer Network, Inc 2016. All rights reserved. Accessed December 1, 2016. To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN GUIDELINES, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.

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)

Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-ineligible Patients

Embryo-fetal Toxicity

Adverse reactions

Please see full Prescribing Information.

Indications