Adding carfilzomib to lenalidomide and dexamethasone adds 9 months of progression-free survival in relapsed multiple myeloma patients with high-risk cytogenetic abnormalities

A subgroup analysis of the phase III ASPIRE study, assessing the addition of carfilzomib to lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma (MM), demonstrates that patients with high-risk cytogentic abnormalities have a 9-month longer progression-free survival (PFS) when carfilzomib is added to Rd. In patients with standard-risk cytogenetics, the PFS benefit of adding carfilzomib was 10 months. In addition, the presented subgroup analysis showed that adding carfilzomib to Rd also led to higher response rates, greater response depth, and a longer duration of response (DoR) both in patients with high- and standard-risk cytogenetics. As such, carfilzomib-Rd has a favorable benefit-risk profile in patients with relapsed MM, irrespective of the baseline cytogenetic risk status. The phase 3 ASPIRE study previously demonstrated a significantly longer PFS when carfilzomib was added to Rd in 792 patients with relapsed MM. For a detailed schedule of the ASPIRE study design we refer to slide 1 in the ‘Keyslides’ attached to this article. During the 2015 annual ASH meeting, a pre-planned subgroup analysis was presented evaluating the efficacy and safety of carfilzomib-Rd as compared to Rd in function of the baseline cytogenetic risk status.

The cytogenetic risk status of patients in ASPIRE was assessed using fluorescence in situ hybridization (FISH). The high-risk group consisted of patients with a t(4;14) or t(14;16), or with a deletion of 17p detected in at least 60% of plasma cells. The standard-risk group consisted of all other patients with known baseline cytogenetics. In patients with known baseline cytogenetics, the baseline cytogenetic risk status was equally divided between the treatment arms with 24,6% and 24,6% of high-risk patients in the carfilzomib-Rd arm and de Rd alone arm, respectively. All baseline patient and disease characteristics were similar for both the standard- and the high-risk patients, except for age. Not surprisingly, patients with the standard-risk cytogenetics had a median age of 66 years, while patients with the high-risk cytogenetics had a median age of 60.5 years.

In the overall study population, carfilzomib-Rd was associated with a median PFS of 26.3 months as compared to 17.6 months with Rd alone (HR [95%CI]: 0.69 [0.57-0.83]; p< 0.001). This magnitude in PFS advantage was also seen in the group of patients with high- and standard-risk cytogenetics (in high-risk: median PFS 23.1 versus 13.9 months, HR [95%CI]: 0.639 [0.369–1.106]; in standard-risk: median PFS 29.6 versus 19.5 months, HR [95%CI]: 0.657 [0.480–0.901]). The overall response rates with carfilzomib-Rd and Rd were 79.2% and 59.6% respectively in the high-risk group, and 91.2% and 73.5% respectively in the standard-risk group. In the high-risk group, 29.2% of patients treated with carfilzomib-Rd achieved a complete response (CR) compared to 5.8% with Rd alone. In the high-risk group, the rate of stringent CR (sCR) was 16.7% with carfilzomib-Rd versus 3.8% with Rd. In the standard-risk group, 38.1% and 6.5% of patients respectively on carfilzomib-Rd and Rd achieved at least a CR. The median DoR in the high-risk group was 22.2 months for carfilzomib-Rd as compared to 14.9 months with Rd alone. In the standard-risk group, the median DoR was 30.4 months for carfilzomib-Rd and 20.4 months for Rd. With respect to safety, no new signals were reported and the cytogenetic status did not influence the incidence of certain adverse events. In conclusion, patients with high-risk cytogenetics had a median PFS of nearly 2 years when treated with carfilzomib-Rd. This represents a 9-month improvement relative to the PFS seen in high-risk patients treated with Rd. Similarly, adding carfilzomib to Rd also led to a 10-month improvement in the median PFS of patients with standard-risk cytogenetics. In addition to this the carfilzomib-Rd combination also induced higher response rates, a greater response depth, and a longer DoR as compared to Rd, irrespective of the baseline cytogenetic risk status.


Avet-Loiseau H, Fonseca R, Siegel D, et al. Efficacy and Safety of Carfilzomib, Lenalidomide, and Dexamethasone Vs Lenalidomide and Dexamethasone in Patients with Relapsed Multiple Myeloma Based on Cytogenetic Risk Status: Subgroup Analysis from the Phase 3 Study Aspire (NCT01080391). Presented at ASH 2015; Abstract #731.

Speaker Hervé Avet-Loiseau

Avet Loiseau

Hervé Avet-Loiseau, MD, PhD,
Head of the Laboratory for Genomics in Myeloma, Centre de Recherche en Cancérologie de Toulouse Institut National de la Santé, Toulouse, France


See: Keyslides


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