Response and progression-free survival according to planned treatment duration in patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in the phase III ASPIRE study

Meletios Dimopoulos, Michael Wang, Vladimir Maisnar, Jiri Minarik, William Bensinger, Maria-Victoria Mateos, Mihaela Obreja, Julie Blaedel, Philippe Moreau, Meletios Dimopoulos, Michael Wang, Vladimir Maisnar, Jiri Minarik, William Bensinger, Maria-Victoria Mateos, Mihaela Obreja, Julie Blaedel, Philippe Moreau

Abstract

Background: In ASPIRE, carfilzomib, lenalidomide, and dexamethasone (KRd) significantly improved progression-free survival (PFS) and response rates versus lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma. Per protocol, patients received KRd for a maximum of 18 cycles followed by Rd to progression, so the benefit/risk profile of KRd to progression was not established.

Methods: This post hoc analysis evaluated the efficacy and safety of KRd versus Rd at 18 months from randomization. Cumulative rates of complete response (CR) or better over time and PFS hazard ratio (HR) at 18 months were evaluated for KRd versus Rd. PFS HRs were also assessed according to cytogenetic risk, prior lines of therapy, and prior bortezomib treatment. Cox regression analysis was used to evaluate PFS HRs.

Results: The hazard ratio (HR) for PFS at 18 months was 0.58 versus 0.69 for the overall ASPIRE study. Patients with high-risk cytogenetics, ≥ 1 prior lines of therapy, and prior bortezomib exposure benefited from KRd up to 18 months versus Rd. The HRs for PFS at 18 months in the pre-defined subgroups were lower than those in the overall study. The difference in the proportion of KRd and Rd patients achieving at least a complete response (CR) increased dramatically over the first 18 months and then remained relatively constant. The safety profile at 18 months was consistent with previous findings.

Conclusions: The improved PFS HR at 18 months and the continued increase in CR rates for KRd through 18 cycles suggest that there may be a benefit of continued carfilzomib treatment.

Trial registration: Clinical trials.gov NCT01080391 . Registered 2 March 2010.

Keywords: Clinical research; Clinical trials; Multiple myeloma; Myeloma therapy.

Conflict of interest statement

Authors’ information

Not applicable.

Ethics approval and consent to participate

All patients provided informed consent. The study was performed according to the Declaration of Helsinki. The study protocol, amendments, protocol clarification letters, informed consent forms, subject dosing diaries, advertisements, and health-related quality of life questionnaires were approved by the institutional review boards of all participating institutions.

Consent for publication

Not applicable.

Competing interests

MD—consultancy for Amgen, Celgene, Janssen, Novartis, and Takeda. MW—research funding from Pharmacyclics, Juno Therapeutics, Acerta Pharma, Celgene, BeiGene, Kite Pharma, Onyx, Asana BioSciences, and Janssen; consultancy for Acerta Pharma and Janssen. VM—grants from the Binding Site; personal fees from Amgen, BMS, Celgene, and Janssen-Cilag. JM—no conflicts of interest to disclose. WB—grants and research funding from Celgene and Amgen Inc. M-VM—personal fees from Amgen, Celgene, Janssen, and Takeda. MO and JB—employment and stock ownership in Amgen, Inc. PM—consultancy for Amgen, Bristol-Myers Squibb, Celgene, Janssen, Novartis, and Takeda.

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Figures

Fig. 1
Fig. 1
Cumulative ≥CR rates by time. ≥CR, complete response or better; aData are from safety population: cumulative ≥CR rates achieved according to time from treatment start
Fig. 2
Fig. 2
PFS in KRd patients: ≥CR responders versus

Fig. 3

PFS in KRd patients: ≥CR…

Fig. 3

PFS in KRd patients: ≥CR responders versus a High-risk cytogenetics. b Prior bortezomib…

Fig. 3
PFS in KRd patients: ≥CR responders versus a High-risk cytogenetics. b Prior bortezomib therapy. c One prior line of treatment. d Two or more prior lines of treatment. ≥CR, complete response or better; <CR, less than complete response; KRd, carfilzomib, lenalidomide and dexamethasone; PFS, progression-free survival
Fig. 3
Fig. 3
PFS in KRd patients: ≥CR responders versus a High-risk cytogenetics. b Prior bortezomib therapy. c One prior line of treatment. d Two or more prior lines of treatment. ≥CR, complete response or better; <CR, less than complete response; KRd, carfilzomib, lenalidomide and dexamethasone; PFS, progression-free survival

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