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 

PLEASE SEE THE IMPORTANT SAFETY INFORMATION IN THE SECTION BELOW.

COLLAPSE

IMPORTANT SAFETY INFORMATION

Warning: Skin rash

In clinical studies, nearly all patients (90%) taking Vectibix® experienced skin rash or other skin reactions. Severe or life-threatening skin reactions have been reported.

Skin reactions included (but were not limited to):

  • Acne-like rash
  • Skin rash
  • Nail infections
  • Dry skin
  • Redness
  • Skin peeling
  • Openings in the skin
  • Itching

percent of these patients had severe skin reactions, which involved pain, disfigurement, ulceration, or loss of outer layers of skin. Some patients who developed severe skin reactions also developed infections in the blood, skin, fat, or tissue that sometimes resulted in death.

doctor may decrease your dose, delay your next dose, or stop Vectibix® treatment altogether to manage your side effects. It is important that you tell your doctor right away if you have any skin reactions or any signs of infection (such as chills, fever, or increased redness or swelling of an existing skin reaction).


RAS-Mutant mCRC

with RAS-mutant mCRC should not take Vectibix®. Investigations of the clinical studies that used Vectibix® showed that Vectibix® exposed patients with RAS-mutant mCRC to serious side effects without working to treat cancer.


Low Electrolytes

patients who were taking Vectibix® developed low levels of certain electrolytes, including:

  • Magnesium
  • Calcium
  • Potassium

doctor may check the levels of these electrolytes in your blood while you are on treatment and for 2 months after you finish treatment. Your doctor may add other oral or intravenous medications to your Vectibix® treatment.


Infusion Reactions

Vectibix® is given by infusion into a vein. Some patients may develop an infusion reaction, which can be severe and in rare cases has resulted in death. Infusion reactions developed in 4% of patients in one clinical trial, and 1% of patients experienced serious infusion reactions. Infusion reactions included:

  • Fever
  • Shortness of breath
  • Low blood pressure
  • Chills
  • Throat spasms

on how severe the reaction is, your doctor may decide to slow the rate of the infusion, stop the infusion, or stop your Vectibix® treatment completely.


Kidney problems

Tell your doctor right away if you experience severe diarrhea or dehydration. Some patients treated with Vectibix® and chemotherapy developed kidney failure or other complications because of severe diarrhea and dehydration.

Lung problems

Lung disease, including fatal lung disease, occurred in 1% or less of patients who had taken Vectibix®. Tell your doctor if you have problems breathing, wheezing, or a cough that doesn’t go away or keeps coming back. If you have been told that you have had lung problems in the past, be sure to tell your doctor. Your doctor may decide to stop Vectibix® treatment.

Avoid sunlight

Being in the sun may make skin reactions worse. Wear sunscreen and protective clothing (like a hat), and avoid direct sunlight while you are on treatment with Vectibix®. Tell your doctor if you have new or worsening skin reactions.


Eye problems

Inflammation of the eye and injury to the cornea have been reported. Tell your doctor if you have any vision changes or eye problems.


Do not take with Avastin®

Patients treated with Avastin® (bevacizumab) and Vectibix® together did not live as long and had more serious side effects, such as acne-like rash, diarrhea, dehydration, painful ulcers and mouth sores, and low levels of potassium and magnesium in the blood. Some patients developed blood clots that can travel to the lungs, which can be very serious or even fatal. Do not take Avastin® with Vectibix®.


Avoid pregnancy

Use effective birth control to avoid pregnancy while taking Vectibix® and for 6 months after the last dose. It is possible for a pregnant patient to transfer Vectibix® to an unborn child, which could be harmful to the unborn child.


Avoid breastfeeding

Vectibix® could also be transferred to a child through breast milk. Your doctor may tell you that you should not nurse your baby during Vectibix® therapy and for 2 months after your last dose of Vectibix®.


Pregnancy Surveillance Program

Women who become pregnant during Vectibix® treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program. Women who are nursing during Vectibix® treatment are encouraged to enroll in Amgen’s Lactation Surveillance Program. Call 1 (800) 772-6436 to enroll.


Most common side effects

In clinical studies using Vectibix® alone, the most common side effects were severe skin reactions, nail infections, lack of energy, nausea, and diarrhea. The most common serious side effects were general declining health and blockage of the bowel.

In clinical studies using Vectibix® with FOLFOX, the most commonly reported side effects for wild-type KRAS patients were diarrhea, painful mouth swelling, swelling/redness of the inner lining of the mouth, lack of energy, nail infection, lack of hunger, unusual magnesium and potassium levels in the blood, rash, acne-like rash, severe itching, and dry skin. The most serious side effects reported in Vectibix®-treated wild-type KRAS patients were diarrhea and dehydration.


Talk to your doctor

Tell your doctor right away if you have any side effects such as worsening skin problems, eye problems, fever, chills, breathing problems (such as a cough that doesn’t go away or keeps coming back, wheezing, or shortness of breath), if you develop diarrhea or become dehydrated, or if you become pregnant.


Other medications

Do not change or stop any medications you may be taking (including over-the-counter drugs or supplements you can buy without a prescription) without first speaking with your doctor.

Please read the full Prescribing Information and discuss it with your doctor.

Results by patient type

These data have been compiled to provide an overview of efficacy with respect to one or more characteristics that may apply to this patient type, and certain data may also apply to other patient types represented herein.

These data were compiled from post hoc analyses of the KRd vs Rd and Kd vs Vd studies to provide a categorical overview of efficacy by patient type. The four defined patient types are based on one or more characteristics that may be used to differentiate your patients with relapsed or refractory multiple myeloma.

 

Standard Risk1,2

High Risk1,2

Fit3,4,*

FIT with a
STANDARD RISK

FIT with a
HIGH RISK

Frail3,4,*

FRAIL with a
STANDARD RISK

FRAIL with a
HIGH RISK

FIT with a
STANDARD RISK

FIT with a
HIGH RISK

FRAIL with a
STANDARD RISK

FRAIL with a
HIGH RISK

High Risk1,2

Defined as relapse within 12 months from transplant or progression within the first year of diagnosis, high cytogenetic risk (from FISH) with chromosomal abnormalities (ie, t(4;14), t(14;16), t(14;20), del(17p), 1q gain), R-ISS stage III, high-risk gene expression profiling, and/or high PC S-phase.

Standard Risk1,2

Defined as cytogenetic abnormalities that are not considered high risk (trisomies, t(11;14), t(6;14)), and/or R-ISS stage I.

Fit3,4,*

Defined as a person < 75 years of age, ECOG Performance Status 0-1, no or well-controlled comorbidities, adequate renal and hepatic function, and/or no significant cardiovascular risk factors.

Frail3,4,*

Defined as a person ≥ 75 years of age, ECOG Performance Status of 2 or more, wheelchair bound, having comorbidities (including diabetes or congestive heart failure), renal impairment, and/or hepatic impairment.

KYPROLIS®-based regimens (KRd and Kd) demonstrated superior median progression-free survival vs Rd and Vd, respectively5,†,‡

KRd27 as a triplet therapy

8.7-month increase in median PFS: 26.3 months (KRd) vs 17.6 months (Rd); hazard ratio (KRd/Rd) = 0.69 (95% CI: 0.57-0.83); two-sided P = 0.00015

Kd56 as a doublet therapy

9.3-month increase in median PFS: 18.7 months (Kd) vs 9.4 months (Vd); hazard ratio (Kd/Vd) = 0.53 (95% CI: 0.44-0.65); one-sided P < 0.00015

CI = confidence interval; ECOG = Eastern Cooperative Oncology Group; FISH = fluorescence in situ hybridization; IMWG = International Myeloma Working Group; ISS = International Staging System; Kd = KYPROLIS® (carfilzomib) and dexamethasone; KRd = KYPROLIS® (carfilzomib), lenalidomide, and dexamethasone; PC = plasma cell; Rd = lenalidomide and dexamethasone; R-ISS = Revised International Staging System; Vd = VELCADE® (bortezomib) and dexamethasone.

Analyses by patient characteristic: high-risk/fit

High-risk/fit patient description§

  • This is a patient who is likely to have high cytogenetic risk (as determined by FISH sequencing)
  • Additionally, this patient may be young (< 75 years of age), or older with good physical function (ECOG Performance Status 0-1), and normal renal and hepatic function
  • KRd
High-riskEarly relapse during prior therapy< 70 years of agePrior stem cell transplantPrior bortezomib exposure
PFS and ≥ CR6

PFS

High-risk/fit patient (KRd): 9.2-month increase in progression-free survivalHigh-risk/fit patient (KRd): 9.2-month increase in progression-free survival
PFS, ORR, and Rate of ≥ CR7

PFS

High-risk/fit patient with early relapse during prior therapy (KRd): increase of nearly 11 months in progression-free survivalHigh-risk/fit patient with early relapse during prior therapy (KRd): increase of nearly 11 months in progression-free survival
PFS and ORR8

PFS

High-risk/fit patient aged < 70 years (KRd): increase of 11 months in progression-free survivalHigh-risk/fit patient aged < 70 years (KRd): increase of 11 months in progression-free survival
PFS and ORR9

PFS

High-risk/fit patient with prior stem cell transplant (KRd): increase of nearly 9 months in progression-free survivalHigh-risk/fit patient with prior stem cell transplant (KRd): increase of nearly 9 months in progression-free survival
PFS10
High-risk/fit patient with prior bortezomib exposure (KRd): increase of nearly 8 months in progression-free survivalHigh-risk/fit patient with prior bortezomib exposure (KRd): increase of nearly 8 months in progression-free survival

Analyses by patient characteristic: standard-risk/fit

Standard-risk/fit patient description**

  • This is a patient who most likely does not have high cytogenetic risk (determined by FISH) or high tumor burden at the time of relapse
  • Additionally, this patient may be young (< 75 years of age), or older with good physical function (ECOG Performance Status 0-1), ISS I, and normal renal and hepatic function
  • KRd
Standard-risk< 70 years of ageAt first relapsePrior stem cell transplantPrior bortezomib exposure
PFS and ≥ CR6

PFS

Standard-risk/fit patient (KRd): increase of more than 10 months in progression-free survivalStandard-risk/fit patient (KRd): increase of more than 10 months in progression-free survival
PFS and ORR8

PFS

Standard-risk/fit patient aged < 70 years (KRd): increase of 11 months in progression-free survivalStandard-risk/fit patient aged < 70 years (KRd): increase of 11 months in progression-free survival
PFS and ≥ CR10

PFS

Standard-risk/fit patient at first relapse (KRd): increase of 12 months in progression-free survivalStandard-risk/fit patient at first relapse (KRd): increase of 12 months in progression-free survival
PFS and ORR9

PFS

Standard-risk/fit patient with prior stem cell transplant (KRd): increase of nearly 9 months in progression-free survivalStandard-risk/fit patient with prior stem cell transplant (KRd): increase of nearly 9 months in progression-free survival
PFS10
Standard-risk/fit patient with prior bortezomib exposure (KRd): increase of nearly 8 months in progression-free survivalStandard-risk/fit patient with prior bortezomib exposure (KRd): increase of nearly 8 months in progression-free survival

Analyses by patient characteristic: high-risk/frail

High-risk/frail patient description††

  • This is a patient who is likely to have high cytogenetic risk (as determined by FISH sequencing)
  • Additionally, this patient may be older (≥ 75), ECOG of at least 2, R-ISS II or III, renally impaired, hepatically impaired, wheelchair bound, and have comorbidities such as diabetes
  • KRd
  • Kd
High-riskEarly relapse during prior therapy≥ 70 years of agePrior stem cell transplant
PFS and ≥ CR6

PFS

High-risk/frail patient (KRd): 9.2-month increase in progression-free survivalHigh-risk/frail patient (KRd): 9.2-month increase in progression-free survival
PFS, ORR, and ≥ CR7

PFS

High-risk/frail patient with early relapse during prior therapy (KRd): increase of nearly 11 months in progression-free survivalHigh-risk/frail patient with early relapse during prior therapy (KRd): increase of nearly 11 months in progression-free survival
PFS and ORR8

PFS

High-risk/frail patient aged ≥ 70 (KRd): increase of nearly 8 months in progression-free survivalHigh-risk/frail patient aged ≥ 70 (KRd): increase of nearly 8 months in progression-free survival
PFS and ORR9

PFS

High-risk/frail patient with prior stem cell transplant (KRd): increase of nearly 9 months in progression-free survivalHigh-risk/frail patient with prior stem cell transplant (KRd): increase of nearly 9 months in progression-free survival
High-riskEarly relapse during prior therapyRenal function: CrCL ≥ 15 to < 80 mL/minRenal function: CrCL ≥ 80 mL/minAt first relapsePrior stem cell transplantPrior bortezomib exposurePrior lenalidomide exposure< 65 years of age 65-74 years of age≥ 75 years of age
PFS, ORR, and ≥ CR11

PFS

High-risk/frail patient (Kd): increase of nearly 3 months in progression-free survivalHigh-risk/frail patient (Kd): increase of nearly 3 months in progression-free survival
PFS7
High-risk/frail patient with early relapse during prior therapy (Kd): increase of over 8 months in progression-free survivalHigh-risk/frail patient with early relapse during prior therapy (Kd): increase of over 8 months in progression-free survival
PFS, OS, ORR, and ≥ CR12

PFS

High-risk/frail patient with renal function ≥15 to < 50 mL/min (Kd): increase of 8.4 in median PFS; High-risk/frail patient with renal function 50 to < 80 mL/min (Kd): increase of 9.2 in median PFSHigh-risk/frail patient with renal function ≥15 to < 50 mL/min (Kd): increase of 8.4 in median PFS; High-risk/frail patient with renal function 50 to < 80 mL/min (Kd): increase of 9.2 in median PFSHigh-risk/frail patient with renal function ≥15 to < 50 mL/min (Kd): increase of 16.6 in median OS; High-risk/frail patient with renal function 50 to < 80 mL/min (Kd): median OS was not reachedHigh-risk/frail patient with renal function ≥15 to < 50 mL/min (Kd): increase of 16.6 in median OS; High-risk/frail patient with renal function 50 to < 80 mL/min (Kd): median OS was not reached
PFS, OS, ORR, and ≥ CR12

PFS

High-risk/frail patient with renal function ≥ 80 mL/min (Kd): increase of 5.4 months in median OS. Median PFS was not reachedHigh-risk/frail patient with renal function ≥ 80 mL/min (Kd): increase of 5.4 months in median OS. Median PFS was not reached
PFS and ORR13

PFS

High-risk/frail patient at first relapse (Kd): increase of over 12 months in progression-free survivalHigh-risk/frail patient at first relapse (Kd): increase of over 12 months in progression-free survival
Reduced risk in disease progression or death and ORR9

Reduced risk for progression or death

High-risk/frail patient with prior stem cell transplant (Kd): 39% reduced risk in disease progression or deathHigh-risk/frail patient with prior stem cell transplant (Kd): 39% reduced risk in disease progression or death

(HR = 0.61; 95% CI: 0.47-0.79)
Median PFS has not been reached for Kd vs
10.2 months for Vd

PFS and ORR13

PFS

High-risk/frail patient with prior bortezomib exposure at first relapse (Kd): increase of over 7 months in progression-free survivalHigh-risk/frail patient with prior bortezomib exposure at first relapse (Kd): increase of over 7 months in progression-free survival
PFS and ORR at first relapse13

PFS

High-risk/frail patient with prior lenalidomide exposure at first relapse (Kd): increase of over 5 months in progression-free survivalHigh-risk/frail patient with prior lenalidomide exposure at first relapse (Kd): increase of over 5 months in progression-free survival
PFS, OS, and ORR14,15

PFS

High-risk/frail patient aged < 65 years (Kd): progression-free survivalHigh-risk/frail patient aged < 65 years (Kd): progression-free survival
PFS, OS, and ORR14,15

PFS

High-risk/frail patient aged 65-74 (Kd): increase of over 6 months in progression-free survivalHigh-risk/frail patient aged 65-74 (Kd): increase of over 6 months in progression-free survival
PFS, OS, and ORR14,15

PFS

High-risk/frail patient aged ≥ 75 (Kd): increase of nearly 10 months in progression-free survivalHigh-risk/frail patient aged ≥ 75 (Kd): increase of nearly 10 months in progression-free survival

Analyses by patient characteristic: standard-risk/frail

Standard-risk/frail patient description‡‡

  • This is a patient who most likely does not have high cytogenetic risk (determined by FISH) or high tumor burden at the time of relapse
  • Additionally, this patient may be older (≥ 75), ECOG 2 or more, R-ISS I, renally impaired, hepatically impaired, wheelchair bound, and have comorbidities such as diabetes
  • Kd
Standard-riskAt first relapsePrior bortezomib exposurePrior lenalidomide exposure< 65 years of age65-74 years of age≥ 75 years of age
PFS, ORR, and ≥ CR11

PFS

Standard-risk/frail patient (Kd): progression-free survivalStandard-risk/frail patient (Kd): progression-free survival
PFS and ORR13

PFS

Standard-risk/frail patient at first relapse (Kd): increase of over 12 months in progression-free survivalStandard-risk/frail patient at first relapse (Kd): increase of over 12 months in progression-free survival
PFS and ORR13

PFS

Standard-risk/frail patient with prior bortezomib exposure (Kd): increase of over 7 months in progression-free survivalStandard-risk/frail patient with prior bortezomib exposure (Kd): increase of over 7 months in progression-free survival
PFS and ORR at first relapse13

PFS

Standard-risk/frail patient with prior lenalidomide exposure (Kd): increase of over 5 months in progression-free survivalStandard-risk/frail patient with prior lenalidomide exposure (Kd): increase of over 5 months in progression-free survival
PFS, OS, and ORR14,15

PFS

Standard-risk/frail patient aged < 65 years (Kd): progression-free survivalStandard-risk/frail patient aged < 65 years (Kd): progression-free survival
PFS, OS, and ORR14,15

PFS

Standard-risk/frail patient aged 65-74 years (Kd): increase of over 6 months in progression-free survivalStandard-risk/frail patient aged 65-74 years (Kd): increase of over 6 months in progression-free survival
PFS, OS, and ORR14,15

PFS

Standard-risk/frail patient aged ≥ 75 (Kd): increase of nearly 10 months in progression-free survivalStandard-risk/frail patient aged ≥ 75 (Kd): increase of nearly 10 months in progression-free survival

KRd vs Rd study: A phase 3, randomized, open-label, multicenter superiority study evaluated KYPROLIS® in combination with lenalidomide and dexamethasone (KRd) vs lenalidomide and dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma who had received 1 to 3 prior lines of therapy. 792 patients were randomized in a 1:1 ratio (396 patients to KRd, 396 to Rd). Patients received their randomized study treatment in 28-day cycles until disease progression or unacceptable toxicity occurred. KYPROLIS® was discontinued after Cycle 18. The primary endpoint was progression-free survival (PFS); select secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DoR), and safety.5,16,17

Kd vs Vd study: A phase 3, randomized, open-label, multicenter superiority study compared KYPROLIS® plus dexamethasone (Kd) to VELCADE® plus dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma who had received 1 to 3 lines of therapy. 929 patients were randomized to a 1:1 ratio to receive Kd (n = 464) for 28-day cycles or Vd (n = 465) for 21-day cycles until disease progression or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS). Select secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DoR), and safety.5,18

REFERENCES

1. 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. 2. 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. 3. Palumbo A, Bringhen S, Mateos M-V, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015;125:2068-2074. 4. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-655. 5. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 6. Avet-Loiseau H, Fonseca R, Siegel D, et al. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma. Blood. 2016;128:1174-1180. 7. Mateos M-V, Goldschmidt H, San-Miguel J, et al. Carfilzomib in relapsed or refractory multiple myeloma patients with early or late relapse following prior therapy: a subgroup analysis of randomized phase 3 ASPIRE and ENDEAVOR trials. Hematol Oncol. 2018;36:463-470. 8. Dimopoulos MA, Stewart AK, Masszi T, et al. Carfilzomib, lenalidomide, and dexamethasone in patients with relapsed multiple myeloma categorized by age: secondary analysis from the phase 3 ASPIRE study. Br J Haematol. 2017;177:404-413. 9. Hari P, Mateos M-V, Abonour R, et al. Efficacy and safety of carfilzomib regimens in multiple myeloma patients relapsing after autologous stem cell transplant: ASPIRE and ENDEAVOR outcomes. Leukemia. 2017;31:2630-2641. 10. 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. 11. Chng WJ, Goldschmidt H, Dimopoulos MA, et al. Carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed or refractory multiple myeloma by cytogenetic risk in the phase 3 study ENDEAVOR. Leukemia. 2017;31:1368-1374. 12. Dimopoulos MA, Siegel D, White DJ, et al. Superior efficacy of carfilzomib and dexamethasone (Kd56) vs bortezomib and dexamethasone (Vd) in multiple myeloma (MM) patients with moderate or serious renal failure: a subgroup analysis of the phase 3 ENDEAVOR study. Blood. 2017;130:1845. 13. Moreau P, Joshua D, Chng W-J, et al. Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3 ENDEAVOR study. Leukemia. 2017;31:115-122. 14. Ludwig H, Dimopoulos MA, Moreau P, et al. Carfilzomib and dexamethasone vs bortezomib and dexamethasone in patients with relapsed multiple myeloma: results of the phase 3 study ENDEAVOR (NCT01568866) according to age subgroup. Leuk Lymphoma. 2017;58:2501-2504. 15. Niesvizky R, Ludwig H, Spencer A, et al. Overall survival of relapsed/refractory multiple myeloma patients treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone: results from the phase 3 ENDEAVOR study according to age subgroup. Blood. 2017;130:1885. 16. 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. 17. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142-152. 18. Dimopoulos MA, Goldschmidt H, Niesvizky R, et al. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18:1327-1337. Defined as cytogenetic abnormalities that are not considered high risk (trisomies, t(11;14), t(6;14)), and/or R-ISS stage I.Defined as relapse within 12 months from transplant or progression within the first year of diagnosis, high cytogenetic risk (from FISH) with chromosomal abnormalities (ie, t(4;14), t(14;16), t(14;20), del(17p), 1q gain), R-ISS stage III, high-risk gene expression profiling, and/or high PC S-phase.Defined as a person < 75 years of age, ECOG Performance Status 0-1, no or well-controlled comorbidities, adequate renal and hepatic function, and/or no significant cardiovascular risk factors.Defined as a person ≥ 75 years of age, ECOG Performance Status of 2 or more, wheelchair bound, having comorbidities (including diabetes or congestive heart failure), renal impairment, and/or hepatic impairment.

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.
  • 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.
  • 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.