Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma

Hervé Avet-Loiseau, Rafael Fonseca, David Siegel, Meletios A. Dimopoulos, Ivan Špička, Tamás Masszi, Roman Hájek, Laura Rosiñol, Vesselina Goranova-Marinova, Georgi Mihaylov, Vladimír Maisnar, Maria Victoria Mateos, Michael Wang, Ruben Niesvizky, Albert Oriol, Andrzej Jakubowiak, Jiri Minarik, Antonio Palumbo, William Bensinger, Vishal KukretiDina Ben-Yehuda, A. Keith Stewart, Mihaela Obreja, Philippe Moreau

Research output: Article

65 Citations (Scopus)

Abstract

The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n548; Rd, n552) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standardrisk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients.

Original languageEnglish
Pages (from-to)1174-1180
Number of pages7
JournalBlood
Volume128
Issue number9
DOIs
Publication statusPublished - szept. 1 2016

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Avet-Loiseau, H., Fonseca, R., Siegel, D., Dimopoulos, M. A., Špička, I., Masszi, T., Hájek, R., Rosiñol, L., Goranova-Marinova, V., Mihaylov, G., Maisnar, V., Mateos, M. V., Wang, M., Niesvizky, R., Oriol, A., Jakubowiak, A., Minarik, J., Palumbo, A., Bensinger, W., ... Moreau, P. (2016). Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma. Blood, 128(9), 1174-1180. https://doi.org/10.1182/blood-2016-03-707596