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Amgen Doubles Down on Helping Patients with Multiple Myeloma

Amgen Oncology_Insight

Multiple myeloma is a blood cancer that affects around 125,000 people in the U.S.1 Over the past several years, the multiple myeloma treatment landscape has seen remarkable advancements. Newly approved drugs and treatment regimens are extending life beyond the expectations of patients and physicians. Despite this significant progress, multiple myeloma remains incurable. Patients often have to endure ongoing cycles of relapse and remission and need several therapies throughout the course of their disease.2,3

So, while much has been achieved, there is much still to do to improve the lives of people living with this disease – now and into the future. Amgen is striving to do just that.

A more convenient dosing schedule for KYPROLIS® (carfilzomib)

KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.4

While effective treatments are critical for patients living with multiple myeloma, the patient experience with that treatment is also important. One way Amgen has tried to improve the patient experience with KYPROLIS is by providing more convenient administration options. The U.S. Food and Drug Administration approved a once-weekly dosing regimen for a specific combination with KYPROLIS and dexamethasone for patients with relapsed or refractory multiple myeloma.4

Approval of the once-weekly dosing option was based on data from the Phase 3 A.R.R.O.W. trial, which demonstrated that KYPROLIS administered at a once-weekly 70 mg/m2 dose with dexamethasone (once-weekly) achieved superior progression-free survival (PFS) and overall response rates (ORR) versus twice-weekly KYPROLIS administered at a dose of 27 mg/m2 in combination with dexamethasone (twice-weekly).4 The median PFS was 11.2 months for the once-weekly regimen versus 7.6 months for the twice-weekly regimen (HR=0.69; 95 percent CI: 0.54-0.88) in patients who had relapsed and refractory MM and received 2-3 prior lines of therapy. The overall safety profile of the two arms were comparable. It's important to note that the KYPROLIS and dexamethasone 27 mg/m2 given twice-weekly is not an FDA approved dose. 4*

The incidence of grade 3 or higher cardiac failure was numerically lower in the once-weekly arm (2.9 percent) compared with the twice-weekly group (4.3 percent).5 The most common adverse reactions (greater than or equal to 10 percent) in either treatment arm were anemia, thrombocytopenia, neutropenia, diarrhea, nausea, pyrexia, fatigue, asthenia, peripheral edema, respiratory tract infection, pneumonia, bronchitis, back pain, headache, insomnia, cough, dyspnea, and hypertension. In randomized, open-label, multicenter trials for combination therapies, the incidence of cardiac failure events was 8%.4

IMPORTANT SAFETY INFORMATION FOR KYPROLIS

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 administration.
  • Monitor patients for signs or symptoms of cardiac failure or 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 at 1 dose level reduction based on a benefit/risk assessment.

Please see additional Important Safety Information below.

Additional data from A.R.R.O.W. were shared at the 60th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego.

"In the fight against multiple myeloma, we are committed to continued evidence generation and innovation to serve patients," said Karim Iskander, executive medical director of global medical affairs at Amgen. “We’re proud to offer this more convenient dosing schedule of KYPROLIS.”

IMPORTANT DOSING AND ADMINISTRATION INFORMATION FOR KYPROLIS

This new dosing option for KYPROLIS (when administered in combination with dexamethasone)  is administered intravenously as a 30-minute infusion once weekly for three weeks followed by a 13-day rest period as part of a 28-day treatment cycle. KYPROLIS is administered at 20 mg/m2 on Day 1 of Cycle 1 to evaluate tolerability. If tolerated, the target dose of 70 mg/m2 is administered starting on Day 8 of Cycle 1.4 Patients should continue treatment until disease progression or unacceptable toxicity occurs.

Adequate hydration is required prior to dosing in Cycle 1, especially in patients at high risk of tumor lysis syndrome or renal toxicity. The recommended hydration includes both oral fluids and intravenous (IV) fluids. If needed, additional IV fluids should be given following KYPROLIS administration and continued oral and/or IV, as needed. Patients should be monitored for evidence of volume overload and adjust hydration to individual patient needs, especially in patients with or at risk for cardiac failure. Dosing should be modified based on toxicity.4

Please see Dosing & Administration section of the KYPROLIS Prescribing Information for additional information.

IMPORTANT SAFETY INFORMATION FOR KYPROLIS

Cardiac Toxicities

• 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.

• For 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 prior to starting treatment with KYPROLIS and remain under close follow-up with fluid management.

Acute Renal Failure

• Cases of acute renal failure, including some fatal renal failure events, and renal insufficiency adverse events (including renal failure) have occurred. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.

Tumor Lysis Syndrome

• Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred. Patients with a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly, and withhold until resolved.

Pulmonary Toxicity

• Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred. Some events have been fatal. In the event of drug‐induced pulmonary toxicity, discontinue KYPROLIS.

Pulmonary Hypertension

• Pulmonary arterial hypertension (PAH) was reported. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS for PAH until resolved or returned to baseline and consider whether to restart based on a benefit/risk assessment.

Dyspnea

• Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart based on a benefit/risk assessment.

Hypertension

• Hypertension, including hypertensive crisis and hypertensive emergency, has been observed, some fatal.  Control hypertension prior to starting KYPROLIS. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS and evaluate. Consider whether to restart based on a benefit/risk assessment.

Venous Thrombosis

• Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed. Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.

• Patients using hormonal contraception associated with a risk of thrombosis should consider an alternative method of effective contraception during treatment.

Infusion Reactions

• Infusion reactions, including life‐threatening reactions, have occurred. Symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration. Premedicate with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risk and of symptoms and seek immediate medical attention if they occur.

Hemorrhage

• Fatal or serious cases of hemorrhage have been reported. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate.

Thrombocytopenia

• KYPROLIS causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Monitor platelet counts frequently during treatment. Reduce or withhold dose as appropriate.

Hepatic Toxicity and Hepatic Failure

• Cases of hepatic failure, including fatal cases, have occurred. KYPROLIS can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate.

Thrombotic Microangiopathy

• Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome have occurred. Monitor for signs and symptoms of TTP/HUS. Discontinue if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The safety of reinitiating KYPROLIS is not known.

Posterior Reversible Encephalopathy Syndrome (PRES)

• Cases of PRES have occurred in patients receiving KYPROLIS. If PRES is suspected, discontinue and evaluate with appropriate imaging. The safety of reinitiating KYPROLIS is not known.

Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-ineligible Patients

• In a clinical trial of transplant-ineligible patients with newly diagnosed multiple myeloma comparing KYPROLIS, melphalan, and prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher incidence of serious and fatal adverse events was observed in patients in the KMP arm. KMP is not indicated for transplant-ineligible patients with newly diagnosed multiple myeloma.

Embryo-fetal Toxicity

• KYPROLIS can cause fetal harm when administered to a pregnant woman.

• Females of reproductive potential should be advised to avoid becoming pregnant while being treated with KYPROLIS and for 6 months following the final dose. Males of reproductive potential should be advised to avoid fathering a child while being treated with KYPROLIS and for 3 months following the final dose.  If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.

ADVERSE REACTIONS

• The most common adverse reactions in the combination therapy trials: anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper respiratory tract infection, hypokalemia.

Please see accompanying full Product Information.

* Kd once-weekly vs twice-weekly study design: Phase 3, randomized, multicenter, open-label study (N = 478) in patients with relapsed and refractory multiple myeloma who had received 2 to 3 lines of therapy, KYPROLIS®+dexamethasone 70 mg/m2 once weekly (n = 240) versus KYPROLIS®+dexamethasone 27 mg/m2 twice weekly (n = 238). The primary endpoint was PFS. Secondary endpoints included ORR and safety.

 

USA-171-80481

  1. National Cancer Institute. Myeloma Cancer Stat Facts. Available at: https://seer.cancer.gov/statfacts/html/mulmy.html. Accessed  November 26, 2018.
  2. American Cancer Society. Survival Rates by Stage for Multiple Myeloma. Available at: https://www.cancer.org/cancer/multiple-myeloma/detection-diagnosis-staging/survival-rates.html. Accessed November 26, 2018.
  3. Kurtin SE. Relapsed or relapsed/refractory multiple myeloma. J Adv Pract Oncol. 2013;4(suppl 1):5-14.
  4. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 
  5. Moreau P, Mateos M-V, Berenson JR, et al. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study. Lancet Oncol. 2018;19:953-964.

This article was created in collaboration with the sponsoring company and our sales and marketing team. The editorial team does not contribute.