A phase 2 single-center study of carfilzomib 56 mg/m2 with or without low-dose dexamethasone in relapsed multiple myeloma

Blood

Volumn 124, Issue 6, 2014, Pages 899-906

  Lendvai, Nikoletta ^a,b   Hilden, Patrick ^a   Devlin, Sean ^a   Landau, Heather ^a,b   Hassoun, Hani ^a,b   Lesokhin, Alexander M ^a,b   Tsakos, Ioanna ^a   Redling, Kaitlyn ^a   Koehne, Guenther ^a,b   Chung, David J ^a,b   Schaffer, Wendy L ^a,b   Giralt, Sergio A ^a,b  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACICLOVIR; ALANINE AMINOTRANSFERASE; ALLOPURINOL; ANTHRACYCLINE; ASPARTATE AMINOTRANSFERASE; BORTEZOMIB; CARFILZOMIB; DEXAMETHASONE; DIURETIC AGENT; LENALIDOMIDE; PALONOSETRON; THALIDOMIDE; ANTINEOPLASTIC AGENT; BORONIC ACID DERIVATIVE; OLIGOPEPTIDE; PYRAZINE DERIVATIVE;

ACUTE KIDNEY FAILURE; ADD ON THERAPY; ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALLOGENEIC STEM CELL TRANSPLANTATION; ANEMIA; ANTIBIOTIC PROPHYLAXIS; ARTHRALGIA; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; AUTOLOGOUS STEM CELL TRANSPLANTATION; BRAIN HEMORRHAGE; CANCER COMBINATION CHEMOTHERAPY; CANCER FATIGUE; CANCER GROWTH; CANCER RECURRENCE; CANCER SURVIVAL; CARDIOGENIC SHOCK; CAUSE OF DEATH; CLINICAL ARTICLE; CONSTIPATION; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG WITHDRAWAL; DYSPNEA; FEBRILE NEUTROPENIA; FEMALE; FOLLOW UP; HEART FAILURE; HERPES ZOSTER; HUMAN; HYPERGLYCEMIA; HYPERTENSION; HYPERVOLEMIA; HYPOCALCEMIA; HYPONATREMIA; HYPOPHOSPHATEMIA; LEUKOPENIA; LOW DRUG DOSE; LYMPHOCYTOPENIA; MALE; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUROPATHY; NEUTROPENIA; OPEN STUDY; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PERIPHERAL EDEMA; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEINURIA; RASH; RESPIRATORY FAILURE; SEPTIC SHOCK; SIDE EFFECT; SINGLE BLIND PROCEDURE; STOMACH ULCER; SYSTOLIC DYSFUNCTION; THROMBOCYTOPENIA; THROMBOTIC THROMBOCYTOPENIC PURPURA; TREATMENT RESPONSE; TUMOR LYSIS SYNDROME; UPPER RESPIRATORY TRACT INFECTION; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; DISEASE COURSE; DISEASE FREE SURVIVAL; GENETICS; KAPLAN MEIER METHOD; MIDDLE AGED; RISK FACTOR; TREATMENT OUTCOME; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BORONIC ACIDS; DEXAMETHASONE; DISEASE PROGRESSION; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; MALE; MIDDLE AGED; MULTIPLE MYELOMA; OLIGOPEPTIDES; PYRAZINES; RISK FACTORS; THALIDOMIDE; TREATMENT OUTCOME;

EID: 84905728163     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2014-02-556308     Document Type: Article

References (31)

1. Demo SD, Kirk CJ, Aujay MA, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 2007;67(13): 6383-6391. (Pubitemid 47037522)
2. 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(9):3281-3290. (Pubitemid 350106321)
3. 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(16):3439-3447.
4. Suzuki E, Demo S, Deu E, et al. Molecular mechanisms of bortezomib resistant adenocarcinoma cells. PLoS ONE. 2011;6(12): e27996.
5. 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(14):2817-2825.
6. Vij R, Wang M, Kaufman JL, et al. An open-label, single-arm, phase 2 (PX-171-004) study of singleagent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood. 2012;119(24):5661-5670.
7. Vij R, Siegel DS, Jagannath S, et al. An openlabel, 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(6):739-748.
8. Jagannath S, Vij R, Stewart AK, et al. An openlabel 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(5):310-318.
9. Badros AZ, Vij R, Martin T, et al. Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety. Leukemia. 2013; 27(8):1707-1714.
10. 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(9):2734-2743.
11. Yang J, Wang Z, Fang Y, et al. Pharmacokinetics, pharmacodynamics, metabolism, distribution, and excretion of carfilzomib in rats. Drug Metab Dispos. 2011;39(10):1873-1882.
12. Papadopoulos KP, Lee P, Singhal S, et al. A phase 1b/2 study of prolonged infusion carfilzomib in patients with relapsed and/or refractory (R/R) multiple myeloma: updated efficacy and tolerability from the completed 20/56 mg/m2 expansion cohort of PX-171-007 [abstract]. Blood. 2011;118(21). Abstract 2930.
13. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348(26): 2609-2617. (Pubitemid 36741588)
14. Jagannath S, Richardson PG, Barlogie B, et al; SUMMIT/CREST Investigators. Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Haematologica. 2006;91(7):929-934. (Pubitemid 44023146)
15. Jagannath S, Barlogie B, Berenson J, et al. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004;127(2):165-172. (Pubitemid 39371809)
16. Mikhael JR, Belch AR, Prince HM, et al. High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program. Br J Haematol. 2009;144(2):169-175.
17. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003;121(5): 749-757.
18. Durie BG, Harousseau JL, Miguel JS, et al; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467-1473. (Pubitemid 44264086)
19. Rajkumar SV, Harousseau JL, Durie B, et al; International Myeloma Workshop Consensus Panel 1. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117(18): 4691-4695.
20. Blad́e J, Samson D, Reece D, et al; Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by highdose therapy and haemopoietic stem cell transplantation. Br J Haematol. 1998;102(5): 1115-1123. (Pubitemid 28435189)
21. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). Available at: http://ctep.cancer.gov/protocolDevelopment/electronic- applications/ctc.htm. Accessed March 21, 2013.
22. Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989;10(1):1-10. (Pubitemid 19099520)
23. Jakubowiak AJ, Siegel DS, Martin T, et al. Treatment outcomes in patients with relapsed and refractory multiple myeloma and high-risk cytogenetics receiving single-agent carfilzomib in the PX-171-003-A1 study. Leukemia. 2013; 27(12):2351-2356.
24. Badros AZ, Papadopoulos KP, Zojwalla N, Lee JR, Siegel DS. A phase 1b study of 30-minute infusion carfilzomib 20/45 and 20/56 mg/m2 plus 40 mg weekly dexamethasone in patients with relapsed and/or refractory (R/R) multiple myeloma [abstract]. Blood. 2012;120(21). Abstract 4036.
25. Siegel D, Martin T, Nooka A, et al. Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies. Haematologica. 2013;98(11): 1753-1761.
26. Kistler KD, Rajangam K, Faich G, Lanes S. Cardiac event rates in patients with newly diagnosed and relapsed multiple myeloma in US clinical practice [abstract]. Blood. 2012;120(21). Abstract 2916.
27. Baker KS, Ness KK, Steinberger J, et al. Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the bone marrow transplantation survivor study. Blood. 2007; 109(4):1765-1772. (Pubitemid 46239613)
28. Armenian SH, Sun CL, Mills G, et al. Predictors of late cardiovascular complications in survivors of hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2010;16(8): 1138-1144.
29. Armenian SH, Sun CL, Vase T, et al. Cardiovascular risk factors in hematopoietic cell transplantation survivors: role in development of subsequent cardiovascular disease. Blood. 2012; 120(23):4505-4512.
30. Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009;53(24): 2231-2247.
31. Robin J, Fintel B, Pikovskaya O, Davidson C, Cilley J, Flaherty J. Multiple myeloma presenting with high-output heart failure and improving with anti-angiogenesis therapy: two case reports and a review of the literature. J Med Case Reports. 2008;2:229.