Efficacy and safety profile of deep responders to carfilzomib-based therapy: a subgroup analysis from ASPIRE and ENDEAVOR

Abstract

To understand the profile of best responders (complete response or better [≥CR]) to carfilzomib, we described the characteristics, progression-free survival (PFS), overall survival (OS) data, and the safety of patients who achieved ≥CR to carfilzomib-based treatment in ASPIRE and ENDEAVOR. In post hoc analyses from ASPIRE and ENDEAVOR, median PFS and OS were longer for ≥CR patients versus those who achieved a very good partial response or partial response (VGPR/PR). In the carfilzomib arm of ASPIRE, median PFS was 50.4 months for ≥CR versus 22.1 months for VGPR/PR; median OS was 67.0 versus 44.2 months, respectively. In the carfilzomib arm of ENDEAVOR, median PFS was 34.0 for ≥CR versus 20.4 months for VGPR/PR; median OS was non-estimable. Despite the longer treatment duration, fewer patients with ≥CR versus VGPR/PR experienced treatment-emergent adverse events that led to discontinuation of carfilzomib-based treatment in ASPIRE or ENDEAVOR. Low serum lactate dehydrogenase was the only factor associated with achieving ≥CR vs patients not achieving CR in ASPIRE in multivariate regression analyses. No association was found between cytogenetic risk status and reaching ≥CR. Carfilzomib treatment may lead to rapid and deep responses, irrespective of most patient characteristics.

Conflict of interest statement

KW has received honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen and Takeda; served in a consulting role for Amgen, Bristol-Myers Squibb, Celgene, Janssen, Juno, Sanofi and Takeda; and received research funding from Amgen, Celgene, Janssen and Sanofi. M-VM has received honoraria from Amgen, Celgene, Janssen and Takeda for lectures and participation in advisory boards. FG has received honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen and Takeda; and served as an advisor for Amgen, Bristol-Myers Squibb, Celgene, Janssen, Roche, Oncopeptides, Abbvie, Adaptive, and Takeda. MD has received honoraria from Amgen, Celgene, Janssen and Takeda for consultancy and advisory boards; and research honoraria from Celgene and Janssen. GC has received research funding and honoraria from Celgene, Janssen and Takeda; and honoraria from Amgen, Bristol-Myers Squibb, GlycoMimetics and Sanofi. ZS is an employee of Amgen (Europe) GmbH and holds Amgen stocks. RD is an employee of Amgen (Europe) GmbH and holds Amgen stocks. LD is an employee of Amgen Ltd and holds Amgen stocks. PM has received honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Millennium, Novartis, Onyx Pharmaceuticals and Takeda; and served in a consulting or advisory role for Amgen, Bristol-Myers Squibb, Celgene, Janssen, Millennium, Novartis, Onyx Pharmaceuticals and Takeda.

Figures

Fig. 1

KM curves for PFS for patients who achieved a best response (≥CR) versus those who achieved VGPR/PR from a the KRd arm of ASPIRE and b the Kd arm of ENDEAVOR. KM estimates of PFS in the carfilzomib arms by response status were obtained using a naïve analysis approach. Caution is warranted when interpreting these naïve analyses owing to the absence of adjustment for bias. ≥CR complete response or better, CI, confidence interval, Kd carfilzomib and dexamethasone, KM Kaplan–Meier, KRd carfilzomib, lenalidomide and dexamethasone, PFS progression-free survival, PR partial response, VGPR very good partial response.

Fig. 2

KM curves for OS for patients who achieved a best response (≥CR) versus those who achieved VGPR/PR from a the KRd arm of ASPIRE and b the Kd arm of ENDEAVOR. KM estimates of OS in the carfilzomib arms by response status were obtained using a naïve analysis approach. Caution is warranted when interpreting these naïve analyses owing to the absence of adjustment for bias. ≥CR complete response or better, CI, confidence interval, Kd carfilzomib and dexamethasone, KM Kaplan–Meier, KRd carfilzomib, lenalidomide and dexamethasone, NE non-estimable, OS overall survival, PR partial response, VGPR very good partial response.