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Kyprolis

Pronunciation

Generic Name: Carfilzomib
Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: (αS) - α - [(4 - Morpholinylacetyl)amino]benzenebutanoyl - l - leucyl - N - [(1S) - 3 - methyl - 1 - [[(2R) - 2 - methyloxiranyl]carbonyl]butyl] - l - phenylalaninamide
Molecular Formula: C40H57N5O7
CAS Number: 868540-17-4

Introduction

Antineoplastic agent; inhibitor of the 20S proteasome.1 2 6 7 8 21 22 23 24

Uses for Kyprolis

Multiple Myeloma

Treatment of multiple myeloma (as monotherapy) in patients who have received ≤2 prior therapies, including bortezomib and an immunomodulatory agent (e.g., lenalidomide, thalidomide) and demonstrated disease progression ≤60 days following completion of their last therapy1 2 14 16 17 (designated an orphan drug by FDA for this use).4

Longer-term maintenance therapy (i.e., more than 12 cycles) was effective and well tolerated in an extension study.18

Overall tolerability profile compares favorably with that of other drugs used in multiple myeloma treatment (e.g., bortezomib, lenalidomide, thalidomide).2 15 18 21 22 23 Appears less likely than bortezomib and thalidomide to cause peripheral neuropathy.2 15 18 21 22 23 Has also been well tolerated in multiple myeloma patients with preexisting peripheral neuropathy.2 21 Incidence of thrombocytopenia appears similar between carfilzomib and bortezomib; carfilzomib causes minimal neutropenia.1 2 23

Kyprolis Dosage and Administration

General

  • Obtain carfilzomib through select specialty distributors and wholesalers.20 For specific information, visit .20

Hydration

  • To minimize risk of nephrotoxicity and tumor lysis syndrome, hydrate patients.1 Maintain adequate fluid volume status throughout therapy; closely monitor blood chemistries.1 (See Tumor Lysis Syndrome under Cautions.)

  • In cycle 1, administration of 250–500 mL of 0.9% sodium chloride injection or other appropriate IV fluid recommended prior to each dose.1 If needed, administer an additional 250–500 mL of IV fluids following administration of carfilzomib.1

  • In subsequent cycles, continue IV hydration as needed.1

  • Monitor patients for fluid overload.1

Premedication

  • To minimize incidence and/or severity of infusion-related reactions, premedicate with dexamethasone 4 mg orally or IV prior to each carfilzomib dose in cycle 1 and prior to each dose during the first cycle of dosage escalation to 27 mg/m2; restart dexamethasone premedication if an infusion-related reaction develops or reappears during subsequent cycles.1 (See Infusion Reactions under Cautions.)

  • Routine antiemetic and antidiarrheal prophylaxis not necessary.6 7

Antiviral Prophylaxis

  • Risk of herpes zoster reactivation.1 Consider antiviral prophylaxis (e.g., acyclovir) in patients with a history of herpes zoster infection.1 22

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer IV.1 Do not administer by rapid IV injection (e.g., IV push or bolus).1

Carfilzomib powder for injection must be reconstituted and may be further diluted prior to administration.1 Use within 24 hours following reconstitution.1 (See Storage under Stability.)

Do not admix with or administer as an IV infusion with any other drug.1

Reconstitution

Reconstitute vial containing 60 mg of carfilzomib with 29 mL of sterile water for injection to provide a solution containing 2 mg/mL; direct diluent toward the wall of the vial.1 Gently swirl and/or slowly invert vial to ensure complete dissolution.1 Do not shake reconstituted solution.1

Reconstituted solution should be clear, colorless, and free of visible particulates.1

Dilution

Dilute appropriate dose in 50 mL of 5% dextrose injection.1 Discard any partially used vial.1

Rate of Administration

Administer by IV injection or infusion over 2–10 minutes.1

Dosage

Adults

Multiple Myeloma
IV

Calculate dosage based on actual BSA at baseline.1 If BSA >2.2 m2, calculate dosage based on BSA of 2.2 m2.1 Dosage adjustment not necessary for weight changes of ≤20%.1

Cycle 1: 20 mg/m2 on 2 consecutive days each week for 3 weeks (days 1, 2, 8, 9, 15, and 16) followed by a 12-day rest period (days 17 through 28).1

Subsequent cycles (if 20 mg/m2 dosage is tolerated in previous cycle): 27 mg/m2 on 2 consecutive days each week for 3 weeks (days 1, 2, 8, 9, 15, and 16) followed by a 12-day rest period (days 17 through 28).1

Continue therapy until disease progression or unacceptable toxicity occurs.1 In principal efficacy study, therapy was continued for a maximum of 12 cycles.2 (See Dosage Modification for Toxicity under Dosage and Administration.)

Because amount of carfilzomib contained in one 60-mg, single-use vial may exceed the single dose required, use caution calculating the dose to prevent overdosage.1

Dosage Modification for Toxicity

Some adverse effects require temporary interruption of therapy and/or dosage reduction.1 If dosage reduction from 27 mg/m2 is necessary, recommended dosage is 20 mg/m2.1 If further dosage reduction is required, recommended dosage is 15 mg/m2.1

Hematologic Toxicity

Monitor platelet counts frequently during therapy.1

If grade 3 or 4 neutropenia or grade 4 thrombocytopenia occurs, withhold therapy.1

If full recovery occurs prior to next scheduled dose, resume therapy at same dosage level.1 If toxicity resolves to grade 2 neutropenia or grade 3 thrombocytopenia, reduce dosage by one dose level.1 If reduced dosage is tolerated, may escalate dosage back to previous dosage at the discretion of the clinician.1 (See Thrombocytopenia under Cautions.)

Cardiac Toxicity

If grade 3 or 4 new-onset or worsening CHF, decreased left ventricular function, or myocardial ischemia occurs, withhold therapy until toxicity resolves or returns to baseline.1

Following resolution, consider whether resuming therapy at a reduced dosage is appropriate based on a benefit/risk assessment.1 If reduced dosage is tolerated, may escalate dosage back to previous dosage at the discretion of the clinician.1 (See Cardiac Effects under Cautions.)

Pulmonary Hypertension

If pulmonary arterial hypertension (PAH) occurs, withhold therapy until toxicity resolves or returns to baseline.1

Consider whether resuming therapy at previous or reduced dosage is appropriate based on a benefit/risk assessment.1 If reduced dosage is tolerated, may escalate dosage back to previous dosage at the discretion of the clinician.1 (See Pulmonary Hypertension under Cautions.)

Pulmonary Complications

If grade 3 or 4 pulmonary complications (e.g., dyspnea) occur, withhold therapy until toxicity resolves or returns to baseline.1

Consider resuming therapy at a reduced dosage.1 If reduced dosage is tolerated, may escalate dosage back to previous dosage at the discretion of the clinician.1 (See Pulmonary Complications under Cautions.)

Hepatic Toxicity

If grade 3 or 4 elevations of serum aminotransferases (ALT or AST), bilirubin, or other liver abnormalities occur, withhold therapy until toxicity resolves or returns to baseline.1

If appropriate, consider resuming therapy at a reduced dosage and frequently monitor liver function tests.1 If reduced dosage is tolerated, may escalate dosage back to previous dosage at the discretion of the clinician.1 (See Hepatic Toxicity and Hepatic Failure under Cautions.)

Nephrotoxicity

If Scr elevations ≥2 times the baseline value occur, withhold therapy until renal function recovers to grade 1 or baseline and monitor renal function.1

If attributable to carfilzomib, resume therapy at reduced dosage.1 If not attributable to carfilzomib, may resume therapy at the dosage used prior to the event.1 If reduced dosage is tolerated, may escalate dosage back to previous dosage at the discretion of the clinician.1

Peripheral Neuropathy

If grade 3 or 4 peripheral neuropathy occurs, withhold therapy until toxicity resolves or returns to baseline.1

May resume therapy at the dosage used prior to the event or at a reduced dosage.1 If reduced dosage is tolerated, may escalate dosage back to previous dosage at the discretion of the clinician.1

Other Nonhematologic Toxicity

If other grade 3 or 4 nonhematologic toxicity occurs, withhold therapy until toxicity resolves or returns to baseline.1

Consider resuming therapy at a reduced dosage.1 If reduced dosage is tolerated, may escalate dosage back to previous dosage at the discretion of the clinician.1

Special Populations

Hepatic Impairment

No specific dosage recommendations.1

Renal Impairment

No dosage adjustment required.1 19

Dialysis: Not studied; administer after dialysis session.1 (See Renal Impairment under Cautions.)

Geriatric Patients

No dosage adjustment required.1 (See Geriatric Use under Cautions.)

Cautions for Kyprolis

Contraindications

  • Manufacturer states none known.1

Warnings/Precautions

Cardiac Effects

Death from cardiac arrest within a day of administration reported.1 2

New onset or worsening of preexisting CHF with decreased left ventricular function or myocardial ischemia also reported.1 2 Heart failure-related events (e.g., CHF, pulmonary edema, decreased left ventricular ejection fraction) occurred in 7% of carfilzomib-treated patients.1

Patients with NYHA class III or IV heart failure, history of MI in the preceding 6 months, or conduction abnormalities not controlled by medication may be at greater risk for cardiac complications.1

Monitor for cardiac complications and manage promptly if they occur.1 If grade 3 or 4 cardiac toxicity occurs, withhold therapy until toxicity resolves or returns to baseline; may resume therapy at reduced dosage if benefit outweighs risk.1 (See Dosage Modification for Toxicity under Dosage and Administration.)

Pulmonary Hypertension

PAH reported in 2% of patients.1 Evaluate patients for PAH using cardiac imaging and/or other tests as indicated.1

If PAH is suspected, withhold therapy until signs and symptoms resolve or return to baseline; may resume therapy at previous or reduced dosage if benefit outweighs risk.1 (See Dosage Modification for Toxicity under Dosage and Administration.)

Pulmonary Complications

Dyspnea reported in approximately 35% of patients.1 2 6 Grade 3 dyspnea occurred in 5% of patients; no grade 4 cases and one fatal case reported.1 2 6 Generally occurs early in therapy and is transient; risk does not increase with cumulative exposure and is not associated with progressive lung injury.2 6

Monitor patients for dyspnea and manage immediately.1 If grade 3 or 4 pulmonary toxicity (i.e., dyspnea) occurs, withhold therapy until toxicity resolves or returns to baseline; may resume therapy at reduced dosage if benefit outweighs risk.1 (See Dosage Modification for Toxicity under Dosage and Administration.)

Infusion Reactions

Infusion-related reactions (e.g., pyrexia, chills, arthralgia, myalgia, flushing, facial edema, emesis, weakness, dyspnea, hypoxia, hypotension, syncope, chest tightness, angina) reported; may occur immediately following or up to 24–48 hours following IV administration.1 5

To minimize incidence and severity of infusion-related reactions, administer premedication with dexamethasone.1 (See Premedication under Dosage and Administration and also see Advice to Patients.)

Tumor Lysis Syndrome

Tumor lysis syndrome reported rarely.1 2 Increased risk in patients with multiple myeloma and high tumor burden.1

Hydrate well prior to administration.1 Some clinicians also concurrently administer allopurinol to reduce risk.22 Monitor for manifestations of tumor lysis syndrome during therapy; if present, manage promptly.1 Interrupt carfilzomib therapy until tumor lysis syndrome resolves.1 (See Hydration under Dosage and Administration.)

Thrombocytopenia

Thrombocytopenia, usually transient and rarely requiring dosage reduction or discontinuance, reported.1 2 Nadir platelet count occurs around day 8 of each 4-week cycle; recovery to baseline typically occurs by start of subsequent cycle.1 2

Monitor platelet counts frequently during therapy.1 If thrombocytopenia occurs, reduce dosage or interrupt therapy as clinically indicated.1 (See Dosage Modification for Toxicity under Dosage and Administration.)

Hepatic Toxicity and Hepatic Failure

Hepatic failure, including fatal cases, reported rarely.1 2 5 6 Elevated serum aminotransferase (ALT or AST) and bilirubin concentrations also reported.1 6

Monitor liver function tests frequently.1 If grade 3 or greater elevations of liver function tests occur, withhold therapy until toxicity resolves or returns to baseline; may resume therapy at reduced dosage if appropriate.1 (See Dosage Modification for Toxicity under Dosage and Administration.)

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryotoxicity and fetotoxicity demonstrated in animals.1

Avoid pregnancy during therapy.1 If used during pregnancy or if the patient becomes pregnant during therapy, apprise of potential fetal hazard.1 (See Advice to Patients.)

Specific Populations

Pregnancy

Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether carfilzomib is distributed into human milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

No clinically important differences in safety and efficacy relative to younger adults.1 (See Absorption: Special Populations, under Pharmacokinetics.)

Hepatic Impairment

Efficacy, safety, and pharmacokinetics not studied in patients with baseline hepatic impairment.1 Patients with baseline ALT or AST concentrations ≥3 times ULN or bilirubin concentrations ≥2 times ULN were excluded from clinical trials.1 2

Renal Impairment

Pharmacokinetics (i.e., clearance, exposure) and safety not affected by baseline mild to severe renal impairment, including chronic hemodialysis; no dosage adjustment necessary.1 19 Because dialysis clearance not specifically studied to date, administer carfilzomib after the hemodialysis session.1

Gender

Pharmacokinetics (e.g., AUC, peak plasma concentrations) not affected by gender.1

Common Adverse Effects

Fatigue,1 2 anemia,1 2 nausea,1 2 dyspnea,1 2 diarrhea,1 2 pyrexia.1 2

Laboratory abnormalities: Anemia,1 2 thrombocytopenia,1 2 increased Scr,1 2 lymphopenia,1 2 neutropenia,1 2 hypokalemia,1 hypomagnesemia,1 leukopenia,1 2 increased AST concentrations,1 hyperglycemia,1 hypercalcemia,1 hypophosphatemia,1 hyponatremia.1

Interactions for Kyprolis

Metabolism appears to occur primarily by extrahepatic peptidase cleavage and epoxide hydrolysis.1 26 CYP-mediated mechanisms play a minor role in overall metabolism.1

Has modest inhibitory effect on CYP3A4/5 in vitro.1 26

Does not induce CYP1A2 or CYP3A4 in human hepatocytes in vitro.1

Substrate of P-glycoprotein (P-gp).1 Has shown marginal inhibitory effects on P-gp in a Caco-2 monolayer system.1

Drugs Affecting Hepatic Microsomal Enzymes

CYP inhibitors or inducers: Clinically important pharmacokinetic interactions unlikely.1 26

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP3A4/5: Clinically important pharmacokinetic interactions not expected.1

Drugs Affecting the P-glycoprotein Transport System

P-gp inhibitors or inducers: Clinically important pharmacokinetic interactions not expected.1

Specific Drugs

Drug

Interaction

Midazolam

No change in pharmacokinetics of midazolam1

Kyprolis Pharmacokinetics

Absorption

Bioavailability

AUC is dose-proportional over the dose range of 20–36 mg/m2.1

Duration

Proteasome inhibition maintained in blood for ≥48 hours following initial dose for each week of dosing.1 26 Duration of proteasome inhibition is longer for carfilzomib than for bortezomib (another proteasome inhibitor), presumably due to carfilzomib's irreversible mechanism of action.1 26

Special Populations

No clinically important difference in exposure between patients ≥65 years of age and younger adults.1

Mild to severe renal impairment, including chronic hemodialysis, does not affect exposure.1 19

Gender does not substantially affect AUC and peak plasma concentrations.1

Distribution

Extent

Not known whether distributed into human milk.1

Plasma Protein Binding

Approximately 97–98%.1 26

Elimination

Metabolism

Rapidly and extensively metabolized; main metabolites were peptide fragments and the diol of carfilzomib, suggesting that peptidase cleavage and epoxide hydrolysis are main metabolic pathways.1 6 26

CYP-mediated mechanisms have a minor role in overall metabolism.1 26

Metabolites have no known pharmacologic activity.1

Elimination Route

Not clearly elucidated in humans.1 Appears to be principally eliminated extrahepatically.1 26

Half-life

≤1 hour following initial IV doses of ≥15 mg/m2.1 7

Special Populations

Effect of hepatic impairment on pharmacokinetics of carfilzomib not elucidated.1

Mild to severe renal impairment, including chronic hemodialysis, does not affect clearance.1 19

Stability

Storage

Parenteral

Powder for Injection

2–8°C in original package to protect from light.1

May store reconstituted drug in vial or syringe at 2–8°C or 15–30°C; use within 24 or 4 hours, respectively, of reconstitution.1

May store infusion solution at 2–8°C or 15–30°C; use within 24 or 4 hours, respectively, of reconstitution.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible1

Dextrose 5% in water

Actions

  • Tetrapeptide epoxyketone proteasome inhibitor.1 2 6 7 8 9 21 22 23 24

  • Selectively and irreversibly inhibits the 20S proteolytic core particle within the 26S proteasome1 2 6 7 8 21 (a large protein complex that degrades ubiquitinated proteins),12 which prevents targeted proteolysis and causes proteotoxic stress resulting in cell death.6 7

  • Has antiproliferative and proapoptotic activity in solid and hematologic tumor cells in vitro, including in some bortezomib-resistant cell lines.1 6 8 21 27

  • In animal studies, inhibits proteasome activity in blood and tissue and delays tumor growth in models of multiple myeloma, hematologic, and solid tumors.1

  • Mechanism by which carfilzomib overcomes bortezomib-resistant cell line models and clinical samples not fully elucidated; however, studies suggest that carfilzomib produces more selective, potent, and durable proteasome inhibition than bortezomib.6 7 10 12 14 21 27

  • Mechanism for peripheral neuropathy resulting from proteasome inhibitor therapy not fully elucidated; however, carfilzomib's selectivity for the 26S proteasome and weak activity on other protease classes may help explain the lower incidence of neurotoxicity observed in animal and clinical studies.2 6 8 12 13

Advice to Patients

  • Importance of informing clinician if fever, chills, rigors, chest pain, cough, or swelling of the feet or legs occurs.1

  • Risk of fatigue, dizziness, syncope, and/or hypotension; importance of advising patients to avoid driving or operating machinery if these effects occur.1

  • Risk of dyspnea, which generally occurs within a day of dosing.1 Importance of informing clinician if shortness of breath occurs.1

  • Importance of avoiding dehydration since carfilzomib may cause vomiting and/or diarrhea.1 Importance of informing a clinician if dizziness, lightheadedness, or fainting spells occur.1

  • Risk of fetal harm.1 Necessity of advising women to avoid pregnancy and use effective methods of contraception while receiving therapy.1 Importance of women informing their clinicians immediately if they are pregnant.1 If pregnancy occurs, advise of potential risk to fetus.1

  • Importance of advising women to avoid breast-feeding while receiving carfilzomib therapy.1 If patient wishes to resume breast-feeding following therapy, importance of discussing appropriate timing with clinician.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., CHF, history of MI, conduction abnormalities).1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Commercially available through select specialty distributors and wholesalers.20 For specific information, visit .20

Carfilzomib

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use only

60 mg

Kyprolis

Onyx

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.

References

1. Onyx Pharmaceuticals, Inc. Kyprolis (carfilzomib) for injection prescribing information. South San Francisco, CA; 2012 Jul.

2. Siegel DS, Martin T, Wang M et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012; 120:2817-25. [PubMed 22833546]

4. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P. L. 97-414). Rockville, MD. From FDA website. Accessed 2012 Nov 12.

5. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 202714: Summary review. 2011 Sep 27. From FDA website.

6. Onyx Pharmaceuticals, Inc. NDA 202,714: Kyprolis (carfilzomib for injection) briefing document. 2012 Jun 20. From FDA website.

7. O'Connor OA, Stewart AK, Vallone M et al. A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clin Cancer Res. 2009; 15:7085-91. [PubMed 19903785]

8. Demo SD, Kirk CJ, Aujay MA et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 2007; 67:6383-91. [PubMed 17616698]

9. da Fonseca PC, Morris EP. Structure of the human 26S proteasome: subunit radial displacements open the gate into the proteolytic core. J Biol Chem. 2008; 283:23305-14. [PubMed 18534977]

10. Kuhn DJ, Chen Q, Voorhees PM et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007; 110:3281-90. [PubMed 17591945]

11. Parlati F, Lee SJ, Aujay M et al. Carfilzomib can induce tumor cell death through selective inhibition of the chymotrypsin-like activity of the proteasome. Blood. 2009; 114:3439-47. [PubMed 19671918]

12. Fostier K, De Becker A, Schots R. Carfilzomib: a novel treatment in relapsed and refractory multiple myeloma. Onco Targets Ther. 2012; 5:237-44. [PubMed 23055749]

13. Arastu-Kapur S, Anderl JL, Kraus M et al. Nonproteasomal targets of the proteasome inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clin Cancer Res. 2011; 17:2734-43. [PubMed 21364033]

14. Jagannath S, Vij R, Stewart AK et al. An open-label single-arm pilot phase II study (PX-171-003-A0) of low-dose, single-agent carfilzomib in patients with relapsed and refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2012; 12:310-8. [PubMed 23040437]

15. Vij R, Wang M, Kaufman JL et al. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood. 2012; 119:5661-70. [PubMed 22555973]

16. Hájek R, Bryce R, Ro S et al. Design and rationale of FOCUS (PX-171-011): a randomized, open-label, phase 3 study of carfilzomib versus best supportive care regimen in patients with relapsed and refractory multiple myeloma (R/R MM). BMC Cancer. 2012; 12:415. [PubMed 22992303]

17. Vij R, Siegel DS, Jagannath S et al. An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib. Br J Haematol. 2012; 158:739-48. [PubMed 22845873]

18. Jagannath S, Vij R, Kaufman JL et al. Long-term treatment and tolerability of the novel proteasome inhibitor carfilzomib (CFZ) in patients with relapsed and/or refractory multiple myeloma (R/R MM). Poster presented at the 52rd ASH annual meeting and exposition. Orlando, FL; 2010 Dec 4. Abstract No. 1953.

19. Badros AZ, Vij R, Martin T et al. Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety. Leukemia. 2013; :1-8 [epub ahead of print].

20. Onyx Pharmaceuticals, Inc. Kyprolis (carfilzomib) product information sheet. South San Francisco, CA. Accessed 2013 May 2.

21. Jain S, Diefenbach C, Zain J et al. Emerging role of carfilzomib in treatment of relapsed and refractory lymphoid neoplasms and multiple myeloma. Core Evidence. 2011; 6:43-57. [PubMed 21654882]

22. Kortuem KM, Stewart AK. Carfilzomib. Blood. 2013; 121:893-897. [PubMed 23393020]

23. Thompson JL. Carfilzomib: a second-generation proteasome inhibitor for the treatment of relapsed and refractory multiple myeloma. Ann Pharmacother. 2013; 47:56-62. [PubMed 23300152]

24. Anon. Carfilzomib (Kyprolis) for multiple myeloma. Med Lett Drugs Ther. 2012; 54:103-4. [PubMed 23282792]

26. Wang Z, Yang J, Kirk C et al. Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib. Drug Metab Dispos. 2013; 41:230-7. [PubMed 23118326]

27. Suzuki E, Demo S, Deu E et al. Molecular mechanisms of bortezomib resistant adenocarcinoma cell lines. PLoS One. 2011; 6:e27996 [epub ahead of print]. [PubMed 22216088]

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