For monotherapy, administer Kyprolis intravenously as a 10-minute or 30-minute infusion depending on the regimen as described: for monotherapy using the 20/27 mg/m^2 regimen, administer Kyprolis intravenously as a 10-minute infusion. In Cycles 1 through 12, administer Kyprolis on two consecutive days, each week for three weeks followed by a 12-day rest period. Each 28-day period is considered one treatment cycle. From Cycle 13, omit the Day 8 and 9 doses of Kyprolis. The recommended starting dose of Kyprolis is 20 mg/m^2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 27 mg/m^2 on Day 8 of Cycle 1. Treatment may continue until disease progression or unacceptable toxicity occurs. For the combination regimen with lenalidomide and dexamethasone, administer Kyprolis intravenously as a 10-minute infusion on two consecutive days, each week for three weeks followed by a 12-day rest period. Each 28-day period is considered one treatment cycle. The recommended starting dose of Kyprolis is 20 mg/m^2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 27 mg/m^2 on Day 8 of Cycle 1. From Cycle 13, omit the Day 8 and 9 doses of Kyprolis. Discontinue Kyprolis after Cycle 18. Lenalidomide 25 mg is taken orally on Days 1–21 and dexamethasone 40 mg by mouth or intravenously on days 1, 8, 15, and 22 of the 28-day cycles. Continue treatment until disease progression or unacceptable toxicity occurs.

To determine whether JNK activation is important in mediating carfilzomib-induced apoptosis, RPMI 8226 cells were exposed to a pulse of 100 nM carfilzomib