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 made by Onyx Pharmaceuticals, a subsidiary of Amgen.

The MMRF and its affiliate organization, 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 which lead to the approval of Kyprolis for treating multiple myeloma.


How is Kyprolis used?

Kyprolis® (carfilzomib, Onyx) is a proteasome inhibitor. In the United States, it is approved for use:

  • 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 are enzymes found in cells that 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 with:

  • High-risk myeloma with associated DNA abnormalities
  • History of previous neuropathy (nerve problems)
  • Advanced age (> 65 years old)

It can also be given safely given to patients with reduced kidney function.
Additionally, results from an early study in newly diagnosed patients suggest that the combination of Kyprolis and Revlimid-low-dose dexamethasone is highly effective, with 98% of patients responding to treatment and 42% of patients achieving a stringent complete response.


How is Kyprolis administered?

Kyprolis® (carfilzomib, Onyx) is administered as an injection directly into a vein (intravenously, or IV). During each 28-day treatment cycle, Kyprolis is given over 2 consecutive days each week for 3 weeks, followed by 12 days off. Dosing varies slightly depending on whether Kyprolis is given alone or in combination with other agents.

Single-agent Kyprolis

When used alone, Kyprolis is given as a 10-minute or 30-minute IV infusion, depending on the dosing used.

  • 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 4 times (2 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 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. Patients receive oral Revlimid 25 mg on Days 1 through 21 and oral or IV dexamethasone 40 mg 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 4 times (2 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 as a 30-minute infusion at a starting dose of 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 oral or IV dexamethasone 20 mg 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 low-dose dexamethasone or with Revlimid-low-dose dex 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 due to a reactivation of the herpes zoster virus (the virus that causes chickenpox).

Treatment with Kyprolis is usually continued until disease progression or unless side effects are not tolerated.


What are Kyprolis side effects?

Possible Kyprolis® (carfilzomib, Onyx) side effects depend on an individual’s past health history and on their 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

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
  • Pneumonia

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® (lenalidomide, Celgene) and low-dose dex were:

  • Low red cell count
  • Low platelet counts
  • Shortness of breath
  • Diarrhea
  • Fatigue

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

  • Low platelet counts
  • Low red cell count
  • Diarrhea
  • Fatigue

Additional safety information

Kyprolis can cause other serious side effects, including:

  • Heart complications
  • High blood pressure in the lungs (pulmonary hypertension)
  • Shortness of breath
  • Infusion reactions
  • Tumor lysis syndrome
  • Liver or kidney toxicity
  • Visual or neurological symptoms
  • Harm to a developing fetus

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?

Kyprolis® (carfilzomib, Onyx) clinical trials have revealed positive effects on treating myeloma as well as manageable side effects.

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 II 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 II trial (PX-171-004) involving 165 patients with relapsed or refractory multiple myeloma after 1 to 3 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 never and who had previously received Velcade® (bortezomib, Takeda Oncology).

Of the 129 patients who had never received Velcade, the overall response was 42%. 14% had a very good partial response 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® (lenalidomide, Celgene), 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 compared to patients receiving Revlimid-low-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-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-dex (P<0.0001)
  • Patients in the Kyprolis-low-dose dex group also had a significantly higher overall response rate than the Velcade-low-dose dex group (77% vs. 63%, P<0.0001).
  • Patients receiving Kyprolis-low-dose dex demonstrated improved progression-free survival and overall response rate over those receiving Velcade-low-dose dex regardless of number of previous treatments or previous exposure to either Revlimid or Velcade. [Moreau ASH 2015 Abstract 729]
  • 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 at least 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
  • Kyprolis, melphalan, and prednisone compared with Velcade, melphalan, and prednisone in patients with newly diagnosed myeloma. This international study known as CLARION is the second head-to-head Phase 2 trial comparing Kyprolis and Velcade and has completed enrollment.
  • Kyprolis and dexamethasone given on a once-weekly or a twice-weekly dosing schedule in patients with relapsed and refractory myeloma (ARROW study)
  • KRd compared with Revlimid as maintenance therapy after autologous stem cell transplantation [NCT02659293]

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

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