Weekly carfilzomib plus cyclophosphamide and dexamethasone in the treatment of relapsed/refractory multiple myeloma: Final results from the MCRN-003/MYX.1 single arm phase II trial.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Cardiovascular Diseases
/ chemically induced
Cyclophosphamide
/ administration & dosage
Dexamethasone
/ administration & dosage
Drug Administration Schedule
Dyspnea
/ chemically induced
Female
Hematologic Diseases
/ chemically induced
Humans
Infections
/ etiology
Kaplan-Meier Estimate
Male
Middle Aged
Multiple Myeloma
/ drug therapy
Myeloma Proteins
/ analysis
Oligopeptides
/ administration & dosage
Patient Selection
Prognosis
Progression-Free Survival
Recurrence
Salvage Therapy
Treatment Outcome
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
01 05 2021
01 05 2021
Historique:
revised:
29
01
2021
received:
28
11
2020
accepted:
14
02
2021
pubmed:
3
3
2021
medline:
14
5
2021
entrez:
2
3
2021
Statut:
ppublish
Résumé
The MCRN-003/CCTGMYX.1 is a single arm phase II trial of weekly carfilzomib, cyclophosphamide and dexamethasone (wKCd), exploring a convenient immunomodulator (IMiD)-free regimen in relapsed myeloma. Weekly carfilzomib (20/70 mg/m
Substances chimiques
Myeloma Proteins
0
Oligopeptides
0
carfilzomib
72X6E3J5AR
Dexamethasone
7S5I7G3JQL
Cyclophosphamide
8N3DW7272P
Banques de données
ClinicalTrials.gov
['NCT02597062']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
552-560Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122-1128.
Venner CP, Connors JM, Sutherland HJ, et al. Novel agents improve survival of transplant patients with multiple myeloma including those with high-risk disease defined by early relapse (<12 months). Leuk Lymphoma. 2011;52(1):34-41.
Breckenridge ZM, Jimenez-Zepeda V, Bahlis NJ, Blood PN. The evolving impact on survival outcomes in multiple myeloma with greater access to novel treatment regimens: experience in a real-world cohort. Blood. 2017;130(suppl 1):1859.
Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2011;26(1):149-157.
Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(14):1319-1331.
Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142-152.
Dimopoulos MA, Terpos E, Boccadoro M, et al. Apollo: phase 3 randomized study of subcutaneous daratumumab plus pomalidomide and dexamethasone (D-Pd) versus pomalidomide and dexamethasone (Pd) alone in patients (Pts) with relapsed/refractory multiple myeloma (RRMM). Blood. 2020;136(suppl 1):5-6.
Siegel DS, Schiller GJ, Samaras CJ, et al. Pomalidomide, dexamethasone, and daratumumab after lenalidomide treatment in relapsed refractory multiple myeloma: updated results from an open-label, multicenter, phase 2 trial. Blood. 2020;136(suppl 1):16-17.
Sebag M, Bahlis N, Venner CP, et al. A randomized phase II, open label, study of daratumumab, weekly low-dose oral dexamethasone and cyclophosphamide with or without pomalidomide in patients with relapsed and refractory multiple myeloma. Blood. 2019;134(suppl 1):3121.
Grammatico S, Bringhen S, Vozella F, Siniscalchi A, Boccadoro M, Petrucci MT. Bortezomib, melphalan, and prednisone in elderly relapsed/refractory multiple myeloma patients: update of multicenter, open-label phase 1/2 study. Leuk Lymphoma. 2017;58(11):2738-2740.
Petrucci MT, Levi A, Bringhen S, et al. Bortezomib, melphalan, and prednisone in elderly patients with relapsed/refractory multiple myeloma: a multicenter, open label phase 1/2 study. Cancer. 2013;119(5):971-977.
Reece DE, Trieu Y, Masih-Khan E, et al. Cyclophosphamide and bortezomib with prednisone or dexamethasone for the treatment of relapsed and refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2016;16(7):387-394.
Popat R, Oakervee H, Williams C, et al. Bortezomib, low-dose intravenous melphalan, and dexamethasone for patients with relapsed multiple myeloma. Br J Haematol. 2009;144(6):887-894.
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(8):728-734.
Dimopoulos MA, Moreau P, Palumbo A, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17(1):27-38.
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(10):1327-1337.
Bringhen S, Mina R, Petrucci MT, et al. Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase I/II studies. Haematologica. 2019;104(8):1640-1647.
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(7):953-964.
Berenson JR, Cartmell A, Bessudo A, et al. CHAMPION-1: a phase 1/2 study of weekly carfilzomib and dexamethasone for relapsed or relapsed and refractory multiple myeloma. Blood. 2016;127(26):3360-3368.
Bringhen S, Rossi D, Larocca A, et al. Weekly carfilzomib, cyclophosphamide and dexamethasone (wCCyd) in elderly newly diagnosed multiple myeloma patients: results of a phase 2 study. Blood. 2015;126(23):1828-1828.
Moreau P, Stewart KA, Dimopoulos M, et al. Once-weekly (70 mg/m2) vs twice-weekly (56 mg/m2) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: a post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials. Cancer Med. 2020;9(9):2989-2996.
Dimopoulos MA, Niesvizky R, Weisel K, et al. Once- versus twice-weekly carfilzomib in relapsed and refractory multiple myeloma by select patient characteristics: phase 3 A.R.R.O.W. study subgroup analysis. Blood Cancer J. 2020;10(3):35.
Biran N, Siegel D, Berdeja JG, et al. Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: a phase 1b study. Am J Hematol. 2019;94(7):794-802.
Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-e548.
Cockcroft D.W, Gault M.H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41.
Rajkumar SV, Harousseau J-L, Durie B, et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117(18):4691-4695.
Monteith B, Venner C, Reece D, et al. Unusual carfilzomib toxicity: three cases of drug-induced thrombotic microangiopathy (TMA) after treatment with high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone (wCCD). Clin Lymphoma Myeloma Leuk. 2019;19(10):e272-e273.
Montefusco V, Corso A, Galli M, et al. Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse. Br J Haematol. 2020;188(6):907-917.
Yong K, Hinsley S, Sherratt D, et al. Carfilzomib versus bortezomib in combination with cyclophosphamide and dexamethasone for treatment of first relapse or primary refractory multiple myeloma (MM): outcomes based on genetic risk and long term follow up of the phase 2 Muk five study. Blood. 2018;132(suppl 1):306.
Mateos M-V, Ocio EM, Balari AS, et al. Randomized phase 2 study of weekly carfilzomib 70 mg/m2 and dexamethasone plus/minus cyclophosphamide in relapsed and/or refractory multiple myeloma (RRMM) patients (GEM-KyCyDex). Blood. 2020;136(suppl 1):8-9.
Moreau P, Joshua D, Chng WJ, 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. 2016;31(1):115-122.
Reece DE, Masih-Khan E, Atenafu EG, et al. Treatment of myeloma patients progressing on lenalidomide-based maintenance after ASCT performed as part of 1st, 2nd or 3rd line therapy: real-world results from the National Myeloma Canada Research Network (MCRN) database. Blood. 2019;134(suppl 1):3173.
Mateos M-V, Sonneveld P, Hungria V, et al. Daratumumab, bortezomib, and dexamethasone versus bortezomib and dexamethasone in patients with previously treated multiple myeloma: three-year follow-up of CASTOR. Clin Lymphoma Myeloma Leuk. 2020;20(8):509-518.
Moreau P, Dimopoulos M-A, Mikhael J, Yong K, Capra M, Facon T, et al. Isatuximab plus carfilzomib and dexamethasone vs carfilzomib and dexamethasone in relapsed/refractory multiple myeloma (IKEMA): interim analysis of a phase 3, randomized, open-label study. In: European Haematology Association Annual Congress; 2020.
Dimopoulos M, Quach H, Mateos M-V, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020;396(10245):186-197.
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(4):e554-e554.
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(9):1174-1180.
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;126(6):1368-1374.
Portuguese AJ, Lipe B. Carfilzomib-induced aHUS responds to early eculizumab and may be associated with heterozygous CFHR3-CFHR1 deletion. Blood Adv. 2018;2(23):3443-3446.
Blasco M, Martínez-Roca A, Rodríguez-Lobato LG, et al. Complement as the enabler of carfilzomib-induced thrombotic microangiopathy. Br J Haematol. 2020; 193(1):181-187. https://doi.org/10.1111/bjh.16796.