Indications
  • 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.
  • KYPROLIS® is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
  • ... Read More 
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KRd vs Rd study results

Median PFS

Superior median progression-free survival: 26.3 months for KRd vs 17.6 months with Rd1

Adding KYPROLIS® to Rd significantly increased median PFS survival by 8.7 months1

Primary endpoint: progression-free survival1
Superior median progression-free survival: 26.3 months for KRd vs 17.6 months with RdSuperior median progression-free survival: 26.3 months for KRd vs 17.6 months with Rd
PFS at 18 months

Post hoc analysis: progression-free survival at 18 months was 64.5% with KRd vs 46.6% with Rd alone1,3

Progression-free survival at 18 months1,3
Post hoc analysis: progression-free survival at 18 months was 64.5% with KRd vs 46.6% with Rd alonePost hoc analysis: progression-free survival at 18 months was 64.5% with KRd vs 46.6% with Rd alone
PFS by 1 previous line

Post hoc analysis: at first relapse, KRd demonstrated a 12-month increase in median progression-free survival over Rd alone4

1 previous line of therapy4
Post hoc analysis: at first relapse, KRd demonstrated a 12-month improvement in median progression-free survival over Rd alonePost hoc analysis: at first relapse, KRd demonstrated a 12-month improvement in median progression-free survival over Rd alone
PFS by 2 or 3 previous lines

Post hoc analysis: KRd demonstrated a 9.1-month increase in median progression-free survival over Rd alone in patients who had received 2 or 3 previous lines of therapy4

2 or 3 previous lines of therapy4
Post hoc analysis: KRd demonstrated a 9.1-month improvement in median progression-free survival over Rd alone in patients who had received 2 or 3 previous lines of therapyPost hoc analysis: KRd demonstrated a 9.1-month improvement in median progression-free survival over Rd alone in patients who had received 2 or 3 previous lines of therapy
PFS in frail-subgroup patients

Post-hoc analysis: Frail-subgroup patients with KRd experienced mPFS 24.1 months vs 15.9 months with Rd alone12,*,†

Patients’ age, ECOG PS, and medical history (comorbidities) were used to evaluate frailty status12,*

Median PFS

KRd significantly increased median overall survival by 7.9 months vs Rd alone (48.3 months KRd vs 40.4 months Rd alone)1

KRd reduced the risk of death by 21% compared to Rd alone1

Secondary endpoint: overall survival1
KRd significantly increased median overall survival by 7.9 months vs Rd aloneKRd significantly increased median overall survival by 7.9 months vs Rd alone
Response by category

Adding KYPROLIS® to Rd tripled the patient’s chance of achieving a complete response or better (KRd vs Rd)1

Secondary endpoint: responses by category1
Adding K to Rd tripled the patient’s chance of achieving a complete response or better (KRd vs Rd)Adding K to Rd tripled the patient’s chance of achieving a complete response or better (KRd vs Rd)

ORR (≥ PR)
KRd = 87% (95% CI: 0.83-0.90)
Rd = 67% (95% CI: 0.62-0.71)
P < 0.0001, two-sided

IMWG uniform response criteria5
ResponseMultiple myeloma response criteria
Stringent complete response (sCR)CR as defined below plus normal free light chain (FLC) ratio* and absence of clonal cells in bone marrow biopsy by immunohistochemistry
Complete response (CR)Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates
Very good partial response (VGPR)Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 hours
Partial response (PR)

≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg/24 hours

If the serum and urine M-protein are unmeasurable, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria

If serum and urine M-protein are unmeasurable, and serum free light assay is also unmeasurable, ≥ 50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥ 30%. In addition to these criteria, if present at baseline, a ≥ 50% reduction in the size (SPD) of soft tissue plasmacytomas is also required

≥ CR over time

Post hoc analysis: adding KYPROLIS® to Rd led to an increase in the rate of ≥ CR6

In a post hoc analysis of CR over time, ≥ CR rates were higher for KRd vs Rd across all time points, reaching 31.9% (KRd) vs 9.3% (Rd) at 30 months after the start of treatment6

Cumulative rates of ≥ CR6
Post hoc analysis: complete response over timePost hoc analysis: complete response over time
≥ CR at 1st relapse

Post hoc analysis: complete response rates at first relapse (KRd vs Rd study)4

≥ CR at first relapse4
Post hoc analysis: complete response rates at first relapsePost hoc analysis: complete response rates at first relapse

Addition of KYPROLIS® to Rd improves PFS and OS while maintaining health-related quality of life for patients with RMM1,7

  • KRd showed superior median PFS (26.3 months with KRd vs 17.6 months with Rd; HR = 0.69; 95% CI: 0.57-0.83; P = 0.0001 two-sided)1
  • KRd demonstrated superior median OS (48.3 months with KRd vs 40.4 months with Rd; HR = 0.79; 95% CI: 0.67-0.95; P = 0.0091 two-sided)1
  • Survival was improved while maintaining HRQOL1,7
GHS/QOL scores and mean treatment differences7
Adding K to Rd improved PFS and OS while maintaining health-related quality of life for patients with relapsed multiple myeloma

Stewart AK, et al. J Clin Oncol. 2016;34:3921-3930. Reproduced with permission.
© 2018 American Society of Clinical Oncology. All rights reserved.

  • The QLQ-C30 contains an overall GHS/QOL domain, five functional domains (physical, emotional, cognitive, social, and role functioning), and nine symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties)7
  • Evidence for development and psychometric quality of the scale is available across a large body of peer-reviewed published literature8-10
  • Validity of the QLQ-C30 has been demonstrated for patients with multiple myeloma8-10
  • Compliance was calculated using the proportion of randomly assigned patients (intent-to-treat population) and the proportion of patients expected to have an assessment (alive and on study treatment)7
    • Logistic regression models were used to explore relationships between the probability of missing data and baseline scores (baseline models) and between the probability of missing data and previous scores (previous value models)7
  • Comparisons between treatment groups were analyzed using a restricted maximum likelihood-based mixed model for repeated measures (MMRM) under the assumption of missing data at random7
  • GHS/QOL was assessed against an overall one-sided significance level of P = 0.025 (two-sided significance level of P = 0.05) under fixed sequence hierarchical testing procedure to adjust for multiplicity7
    • At the time of analysis, the reported P values were considered descriptive and unadjusted for multiplicity, because OS data were not mature at that point, so the GHS/QOL endpoint was not to be tested. Since this analysis, superiority of KRd OS over Rd has been established
  • Open-label design—patients were aware of their treatment allocation before completing their baseline assessment7
  • Differential attrition across groups7
  • GHS/QOL scores account for only 1 aspect of HRQOL. The GHS/QOL domain alone is not adequate to fully assess the broad and multidimensional concept of HRQOL
  • Least mean scores were adjusted for baseline score, baseline score by visit interaction, and random assignment stratification factors (baseline ß2-microglobulin levels, prior bortezomib, and prior lenalidomide)7
  • A minimally important difference (MID) represents the smallest group-level difference in a PRO score considered clinically meaningful, and an MID of 5 points for between-group differences on the QLQ-C30 GHS/QOL was prespecified7
  • An MID of 5 points is not universally agreed upon as the value for indicating a clinically meaningful change11
  • Only GHS/QOL scores exhibited statistical significance from the QLQ-C307
    • GHS/QOL reached the MID of 5 points only at cycle 127

Meet Elizabeth, a 66-year-old African American female

Hypothetical KRd case study of a standard-risk* patient with multiple myeloma at first relapse

Time for a deep and durable response
  • Retired nurse with active, healthy lifestyle
  • Hypertension well controlled with medication
  • M-protein levels monitored regularly
  • Standard-risk cytogenetics*
  • ECOG PS 1
Not an actual patient

Dr. Berenson expert video

When multiple myeloma relapses, see why Dr. James Berenson chooses KRd for his patients

Dr. James Berenson expert video on choosing KRd for patients when multiple myeloma relapses

KRd vs Rd phase 3 design: (N = 792) randomized (1:1), open-label superiority study in relapsed or refractory multiple myeloma patients who had received 1 to 3 prior lines of therapy. The primary endpoint was progression-free survival. Select secondary endpoints included overall survival and overall response rate.1,15,16

Per protocol, patients received 18 cycles of KYPROLIS® with Rd, unless discontinued for toxicity or disease progression, and then continued treatment with Rd alone to progression or unacceptable toxicity.

REFERENCES

1. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.3.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed March 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. 3. Data on file, Amgen; 2014. 4. Dimopoulos MA, Stewart AK, Masszi T, et al. Carfilzomib-lenalidomide-dexamethasone vs lenalidomide-dexamethasone in relapsed multiple myeloma by previous treatment. Blood Cancer J. 2017;7:e554. 5. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17:e328-e346. 6. Dimopoulos M, Wang M, Maisnar V, et al. Response and progression-free survival according to planned treatment duration in patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in the phase III ASPIRE study. J Hematol Oncol. 2018;11:49. 7. Stewart AK, Dimopoulos MA, Masszi T, et al. Health-related quality-of-life results from the open-label, randomized, phase III ASPIRE trial evaluating carfilzomib, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone in patients with relapsed multiple myeloma. J Clin Oncol. 2016;34:3921-3930. 8. Cocks K, Cohen D, Wisløff F, et al. An international field study of the reliability and validity of a disease-specific questionnaire module (the QLQ-MY20) in assessing the quality of life of patients with multiple myeloma. Eur J Cancer. 2007;43:1670-1678. 9. Wisløff F, Eika S, Hippe E, et al. Measurement of health-related quality of life in multiple myeloma. Br J Haematol. 1996;92:604-613. 10. Kvam AK, Fayers PM, Wisloff F. Responsiveness and minimal important score differences in quality-of-life questionnaires: a comparison of the EORTC QLQ-C30 cancer-specific questionnaire to the generic utility questionnaires EQ-5D and 15D in patients with multiple myeloma. Eur J Haematol. 2011;87:330-337. 11. Cocks K, King MT, Velikova G, Martyn St-James M, Fayers PM, Brown JM. Evidence-based guidelines for determination of sample size and interpretation of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30. J Clin Oncol. 2011;29:89-96. 12. Facon T, Niesvizky R, Weisel K, et al. Carfilzomib in relapsed or refractory multiple myeloma: frailty subgroup analysis from phase 3 ASPIRE and ENDEAVOR. Poster presented at: 17th International Myeloma Workshop; September 12-15, 2019; Boston, MA. 13. The mSMART Clinical Practice Guidelines in relapsed myeloma. Mayo Stratification for Myeloma and Risk-adapted Therapy website. https://nebula.wsimg.com/1c0adc8316c5947bb2b948ad5e9e2e55?AccessKeyId=A0994494BBBCBE4A0363&disposition=0&alloworigin=1. Accessed October 14, 2019. 14. Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised International Staging System for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 2015;33:2863-2869. 15. Siegel DS, Dimopoulos MA, Ludwig H, et al. Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. J Clin Oncol. 2018;36:728-734. 16. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142-152.

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), 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 reactions until recovery, and consider whether to restart at 1 dose level reduction based on a benefit/risk assessment.
  • 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 (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-Related Reactions

  • Infusion-related reactions, including life-threatening reactions, have occurred. Signs and symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, laryngeal 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-related 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.

Progressive Multifocal Leukoencephalopathy (PML)

  • Cases of PML, including fatal cases, have occurred. In addition to KYPROLIS, other contributary factors may include prior or concurrent use of immunosuppressive therapy. Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms. If PML is suspected, discontinue and initiate evaluation for PML including neurology consultation.

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 reactions 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.
  • Advise pregnant women of the potential risk to a fetus. Females of reproductive potential should use effective contraception during treatment with KYPROLIS and for 6 months following the final dose. Males of reproductive potential should use effective contraception during treatment with KYPROLIS and for 3 months following the final dose.

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.
  • The most common adverse reactions in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.

Please see full Prescribing Information.

INDICATIONS

  • 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.
  • KYPROLIS® is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.

Reach out to a KYPROLIS® Field Representative

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