Kyprolis, also known as carfilzomib, is a next-generation proteasome inhibitor in the same drug class as Velcade (bortezomib, Takeda Oncology). Kyprolis is manufactured by Amgen.
The MMRF and the Multiple Myeloma Research Consortium (MMRC) played an integral role in the development of Kyprolis. The MMRC provided clinical trial support and resources, including driving patient enrollment to the study that lead to the approval of Kyprolis for multiple myeloma treatment.
Please visit the sponsor’s official patient site for up-to-date information on Kyprolis.
In the United States, Kyprolis is approved for the following uses in multiple myeloma treatment:
Proteasomes, which are proteins found in cells, play an important role in regulating cell function and cell growth by controlling the breakdown of important proteins. As a proteasome inhibitor, Kyprolis blocks the activity of proteasomes and in turn disrupts processes related to the growth and survival of cancer cells.
Kyprolis has been shown to be effective in patients with relapsed and refractory multiple myeloma following treatment with other available agents, including Velcade and Revlimid. In the trial supporting the initial FDA approval of Kyprolis, 20.1% of patients who did not respond to or could not tolerate Velcade and one or more IMiDs responded to Kyprolis alone.
In addition, Kyprolis has also been shown to be effective in patients who:
Kyprolis can also be given safely given to patients with reduced kidney function.
Results from an early study in newly diagnosed patients suggest that the combination of Kyprolis, Revlimid, and low-dose dexamethasone is highly effective, with 98% of patients responding to treatment and 42% achieving a stringent complete response.
Kyprolis is administered as an intravenous (IV) infusion. Dosing varies depending on whether Kyprolis is given alone or in combination with other agents.
When used alone, Kyprolis is given twice weekly as a 10-minute or 30-minute infusion, depending on the dosing used. Kyprolis is given for 3 weeks on this schedule, followed by 12 days off.
Patients follow either of these schedules for 12 cycles. For Cycle 13 and beyond, patients receive Kyprolis four times (two consecutive days during the first and third weeks).
For patients receiving KRd combination therapy, Kyprolis is administered as a 10-minute infusion given on two consecutive days, each week for 3 weeks, followed by 12 days off. Kyprolis is started at 20 mg/m2 during the first cycle on Days 1 and 2. If this dose is tolerated, the dose is increased to 27 mg/m2 for the remaining cycles. Patients also receive 25 mg of oral Revlimid on Days 1 through 21 and 40 mg of oral or IV dexamethasone on Days 1, 8, 15, and 22 of each cycle.
Patients follow this schedule for 12 cycles. For cycles 13 through 18, patients receive Kyprolis four times (two consecutive days during the first and third weeks). After 18 cycles, Kyprolis is stopped, but patients can continue receiving Revlimid-dex.
When administered in combination with low-dose dexamethasone, Kyprolis is administered once or twice weekly as a 30-minute infusion.
Patients experiencing severe side effects may have Kyprolis temporarily stopped until the side effects resolve and may have their dose reduced when Kyprolis is restarted.
Patients also receive IV fluids (hydration) before and possibly after administration of each dose of Kyprolis during the first treatment cycle, and as needed in the remaining cycles. Hydration helps reduce the risk of damage to the kidneys and of tumor lysis syndrome.
Dexamethasone pre-medication is also given prior to each dose of Kyprolis during the first treatment cycle as well as during any cycle when the dose of Kyprolis is increased. This pre-medication is given to reduce the risk and severity of infusion reactions, a possible side effect seen with some drugs that are given intravenously.
Patients may also receive dexamethasone if they experience symptoms of an infusion reaction.
Patients receiving Kyprolis in combination with Revlimid and/or low-dose dexamethasone may also receive a blood thinner (anticoagulant) to prevent blood clots.
Patients receiving Kyprolis may also receive medication to prevent shingles, a viral infection that causes a painful rash and is caused by a reactivation of the herpes zoster virus (the virus that causes chickenpox).
Treatment with Kyprolis is usually continued until the disease progresses or until the patient experiences intolerable side effects.
Possible Kyprolis side effects depend on an individual’s past health history and on his or her current stage of multiple myeloma.
The most common side effects seen in clinical trials of single-agent Kyprolis were:
The most common serious side effects seen with single-agent Kyprolis in clinical trials were:
The most common side effects seen in the study that led to the approval of Kyprolis in combination with Revlimid and low-dose dex were:
The most common serious side effects seen with Kyprolis-low-dose dex were:
Kyprolis can cause other serious side effects, including:
Patients may experience infusion reactions immediately following or up to 24 hours after receiving Kyprolis. These reactions can include fever, chills, achiness, flushing, facial swelling, vomiting, weakness, shortness of breath, low blood pressure, fainting, chest tightness, and chest pain. However, dexamethasone given prior to Kyprolis reduces the incidence and severity of these reactions.
Importantly, there was a low incidence of peripheral neuropathy in clinical studies and it was generally mild when it occurred.
Patients experiencing severe side effects may have their Kyprolis dose reduced or may have Kyprolis temporarily stopped until the side effects resolve.
Please tell your doctor or nurse if you experience any side effects.
What have Kyprolis clinical trials shown?
In clinical trials, Kyprolis has achieved positive in myeloma patients, and side effects have been shown to be manageable.
Kyprolis was initially granted FDA approval for treatment of patients with relapsed or refractory multiple myeloma based on the results of a large phase 2 study (PX-171-003-A1) involving 266 patients who had received an average of five myeloma therapies prior to entering this trial.
In another phase 2 trial (PX-171-004) involving 165 patients with relapsed or refractory multiple myeloma after one to three therapies, Kyprolis provided one of the highest single-agent response rates and longest response duration reported in this patient population. Results were assessed both for those who had and had not previously received Velcade.
Of the 129 patients who had never received Velcade, the overall response was 42%. A very good partial response was seen in 14%, and 25% had a partial response.
The Multiple Myeloma Research Consortium (MMRC), an affiliate organization of the MMRF that accelerates early-stage clinical trials, played a pivotal role in these clinical studies. For PX-171-003-A1, the MMRC enrolled nearly 60% of patients, yet represented just one third of the total sites. Similarly, in study PX-171-004, MMRC member institutions enrolled approximately 44% of patients who participated.
Kyprolis in combination with Revlimid and dexamethasone
The combination of Kyprolis, Revlimid, and low-dose dexamethasone (KRd) was approved for use in patients with relapsed myeloma based on the results of the ASPIRE trial. This international phase 3 trial included 792 patients who had received one to three prior treatment regimens.
Kyprolis in combination with dexamethasone
An international phase 3 trial known as ENDEAVOR was one of two head-to-head phase 3 trials comparing Kyprolis and Velcade. The study included 929 patients whose myeloma had relapsed after at least one, but not more than three, prior treatment regimens. Patients received either Kyprolis or Velcade in combination with low-dose dexamethasone.
Results from the study show that:
How is Kyprolis currently being studied in myeloma?
Kyprolis is being evaluated in combination with other agents in a number of ongoing clinical trials in relapsed and/or refractory myeloma, as well as in newly diagnosed disease and smoldering multiple myeloma, and as maintenance therapy.
Several phase 3 trials are being conducted, including studies evaluating: