Kyprolis

What is Kyprolis?

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 .


How is Kyprolis used?

In the United States, Kyprolis is approved for the following uses in multiple myeloma treatment:

  • In combination with low-dose dexamethasone (Kd) or with Revlimid (lenalidomide, Celgene) and low-dose dexamethasone (KRd) for the treatment of patients with relapsed multiple myeloma who have received one to three prior treatments
  • As a single agent for patients with relapsed or refractory myeloma who have received one or more lines of therapy

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.

What types of patients can benefit from Kyprolis?

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:

  • Have high-risk myeloma with associated DNA abnormalities
  • Have a history of previous neuropathy (nerve problems)
  • Are >65 years of age

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.


How is Kyprolis administered?

Kyprolis is administered as an intravenous (IV) infusion. Dosing varies depending on whether Kyprolis is given alone or in combination with other agents.

Single-agent Kyprolis

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.

  • For one dosing regimen, Kyprolis is administered as a 10-minute infusion and 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.
  • For the other dosing regimen, Kyprolis is administered as a 30-minute infusion and 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 56 mg/m2 for the remaining cycles.

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).

Kyprolis in combination with Revlimid and dexamethasone

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.

Kyprolis in combination with dexamethasone

When administered in combination with low-dose dexamethasone, Kyprolis is administered once or twice weekly as a 30-minute infusion.

  • For the once-weekly dosing regimen, Kyprolis is administered as a 30-minute infusion once weekly for three weeks followed by a 13-day rest period. Kyprolis is started at 20 mg/m2 during the first cycle on Day 1. If this dose is tolerated, the dose is increased to 70 mg/m2 for the remaining cycles. Patients also receive 40 mg of oral or IV dexamethasone on Days 1, 8, and 15 of all cycles and on Day 22 of Cycles 1 to 9. Dexamethasone is given 30 minutes to 4 hours before Kyprolis is administered.
  • For the twice-weekly dosing regimen, Kyprolis is administered as a 30-minute infusion twice weekly for three weeks followed by a 12-day rest period. 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 56 mg/m2 for the remaining cycles. Patients receive 20 mg of oral or IV dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. Dexamethasone is given 30 minutes to 4 hours before Kyprolis is administered.

Additional information

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.


What are Kyprolis side effects?

Possible Kyprolis side effects depend on an individual’s past health history and on his or her current stage of multiple myeloma.

Single-agent Kyprolis

The most common side effects seen in clinical trials of single-agent Kyprolis were:

  • Fatigue
  • Low red blood cell count (anemia)
  • Nausea
  • Low platelet count (thrombocytopenia)
  • Shortness of breath
  • Diarrhea
  • Fever
  • Headache
  • Cough
  • Swelling of legs and hands

The most common serious side effects seen with single-agent Kyprolis in clinical trials were:

  • Low red blood cell count
  • Low platelet count
  • Low white blood cell count

Kyprolis in combination with Revlimid and dexamethasone

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:

  • Low red cell count
  • Low platelet counts
  • Shortness of breath
  • Diarrhea
  • Fatigue
  • Cough
  • Muscle spasms
  • Respiratory infection
  • Low potassium (hypokalemia)

Kyprolis in combination with dexamethasone

The most common serious side effects seen with Kyprolis-low-dose dex were:

  • Low platelet counts
  • Low red cell count
  • Diarrhea
  • Fatigue
  • Fever, insomnia
  • Shortness of breath
  • Cough

Additional safety information

Kyprolis can cause other serious side effects, including:

  • Heart complications
  • High blood pressure, including in the arteries of the lungs (pulmonary hypertension)
  • Shortness of breath
  • Infusion reactions
  • Tumor lysis syndrome
  • Liver or kidney toxicity
  • Kidney failure
  • Visual or neurological symptoms
  • Harm to a developing fetus
  • Blood clots (venous thrombosis, thrombotic microangiopathy)

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.

Single-agent Kyprolis

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.

  • 24% of patients achieved a partial response or better with Kyprolis
  • On average, responses lasted 7.8 months
  • Average survival was 15.6 months

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 overall response increased to 52% with a higher dose of Kyprolis
  • Responses were durable, lasting a median of 13.1 months
  • In the patients who had previously received Velcade but stopped responding to it, the overall response was 17%
  • Average duration of response was 11.5 months
  • Median time until the disease started to progress was 8.1 months

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.

  • Patients receiving KRd lived 50% longer (8.7 months longer) without their disease worsening than did patients receiving Revlimid andlow-dose dex (Rd) alone.
    • Progression-free survival was 26.3 months in the KRd group compared to 17.6 months in the Rd group.
  • The overall response rate was 87% in the KRd group and 67% in the Rd group.
  • A higher percentage of patients in the KRd group achieved a stringent complete response (sCR) than in the Rd group (14% vs 4%).

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:

  • Patients receiving Kyprolis and low-dose dex lived twice as long without their disease progressing.
    • Progression-free survival was 18.7 months compared with 9.4 months with Velcade and dex (P<0.0001)
  • Patients in the Kyprolis and low-dose dex group also had a significantly higher overall response rate than did those in the Velcade and low-dose dex group (77% vs. 63%, P<0.0001).
  • Patients receiving Kyprolis and low-dose dex demonstrated improved progression-free survival and overall response rate relative to patients receiving Velcade and low-dose dex regardless of the number of previous treatments or previous exposure to either Revlimid or Velcade.
  • Results from this study led to the approval of Kyprolis and low-dose dexamethasone for use in patients with relapsed or refractory myeloma who had received 1 to 3 previous treatments.

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:

  • KRd compared with Velcade-Rd in patients with newly diagnosed myeloma (NCT01863550)
  • KRd compared with Revlimid as maintenance therapy after autologous stem cell transplantation (NCT02659293)
  • Kyprolis, daratumumab and dexamethasone (KdD) in relapsed refractory patients (CANDOR; NCT03158688)
  • Kyprolis, lenalidomide, and dexamethasone vs bortezomib, lenalidomide and dexamethasone (KRd vs VRd) in patients with newly diagnosed multiple myeloma (COBRA; NCT03729804)
  • Kyprolis, isatuximab, and dexamethasone in relapsed refractory patients (IKEMA; NCT03275285)

Interested in learning more about Kyprolis clinical trials? Talk to an MMRF Nurse Patient Navigator to learn more or use our clinical trials finder:

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Updated February 2019

Please visit the sponsor’s official patient site for up-to-date information on Kyprolis