KYPROLIS (carfilzomib) for Injection Menu
KRd vs Rd STUDY DESIGN

Superiority study of KRd vs Rd

KRd = KYPROLIS®, lenalidomide, and dexamethasone; Rd = lenalidomide and dexamethasone.

Overview

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

  • Compared KYPROLIS® plus lenalidomide and dexamethasone (KRd) vs lenalidomide and dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma who had received 1 to 3 lines of therapy1
View the KRd vs Rd study design

­†Predose and postdose hydration was administered in cycle 1 in the KRd arm only.2

  • Patients were stratified according to3:
    • Prior treatment with VELCADE® (bortezomib)
    • Prior treatment with lenalidomide
    • Serum beta-2 microglobulin
  • Primary endpoint was progression-free survival (PFS)3
  • Select secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DoR), and safety3
Baseline characteristics

Baseline characteristics were well-balanced between study arms1,3

Patient demographics and baseline characteristics
Characteristic KRd (n = 396) Rd (n = 396)
Age, years
Median (min, max) 64 (38, 87) 65 (31, 91)
ECOG performance status, n (%)
0 165 (42) 175 (44)
1 191 (48) 186 (47)
2 40 (10) 35 (9)
ISS stage at study baseline, n (%)
I 167 (42) 154 (39)
II 148 (37) 153 (39)
III 73 (18) 82 (21)
Unknown 8 (2) 7 (2)
Risk factors
CrCL, mL/min median (min, max) 79 (39, 212) 79 (30, 208)
30 to < 50 mL/min, n (%) 19 (5) 32 (8)
50 to < 80 mL/min, n (%) 185 (47) 170 (43)
Prior regimens at baseline KRd (n = 396) Rd (n = 396)
Number of prior regimens, median (range) 2 (1-3) 2 (1-3)
Prior therapies, n (%)
Transplantation 217 (55) 229 (58)
VELCADE® 261 (66) 260 (66)
Non-responsive to prior VELCADE®§­ 60 (15) 58 (15)
Lenalidomide 79 (20) 78 (20)
Any IMiD 233 (59) 229 (58)
Refractory to prior IMiD in any prior regimen 85 (22) 88 (22)
VELCADE® and IMiD 146 (37) 139 (35)
Non-responsive to prior VELCADE® and refractory to prior IMiD 24 (6) 27 (7)

ECOG = Eastern Cooperative Oncology Group; ISS = International Staging System; CrCL = creatinine clearance; IMiD = immunomodulatory agent.

One patient in each group received four prior regimens.

§Non-responsive to prior VELCADE® is defined as less than minimal response (MR) to any VELCADE®-containing regimen, disease progression during any VELCADE®-containing regimen, or disease progression within 60 days after the completion of any VELCADE®-containing lines of therapy.

Note: Carfilzomib (KYPROLIS®) in combination with lenalidomide and dexamethasone (KRd) 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.4

References

1. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 2. Data on file, Amgen; 2014. 3. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142-152. 4. 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. 1. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 2. Data on file, Amgen. 3. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142-152.

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