ASH 2017 | Carfilzomib versus bortezomib: phase II MUK Five Study

The MM Hub is pleased to share research findings from the 59th American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia.  On Monday 11 December 2017, the evening oral abstract session took place for Myeloma: Therapy, excluding Transplantation Studies in Relapsed and Refractory Multiple Myeloma.  Prof. Kwee L Yong of UCL Cancer Institute in London, UK presented data from Abstract #835: Carfilzomib, Cyclophosphamide and Dexamethasone (KCD) Versus Bortezomib, Cyclophosphamide and Dexamethasone (VCD) for Treatment of First Relapse or Primary Refractory Multiple Myeloma (MM): First Final analysis of the Phase 2 MUK Five Study. The MM summary here is based on updated data presented at the ASH session and therefore may supersede the data in the pre-published abstract.

The aim of this study was to assess the efficacy of carfilzomib compared to bortezomib in combination with cyclophosphamide and dexamethasone as a second-line therapy.  Patients were randomized to receive 6 cycles of 28 days each KCd or 8 cycles of 21 days each of VCd.  The primary endpoint was greater than or equal to very good partial response (VGPR) measured at 24 weeks. Patients were excluded if they had a significant co-morbidities or cardiovascular disease, uncontrolled hypertension, prior carfilzomib therapy, failed prior bortezomib therapy or had significant neuropathy.

Key Findings:

• Total patients (pts) (n = 300)
  • n = 210 carfilzomib, cyclophosphamide, dexamethasone (KCd)
  • n = 99 bortezomib, cyclophosphamide, dexamethasone (VCd)
• Stratification Factors
  • Prior bortezomib KCd = 21.9% vs VCd = 21.2%
  • Prior ASCT KCd = 66.2% vs VCd = 67.7%
  • β2 microglobulin >5.5mg/L KCd = 13.9% vs VCd = 15.2%
• Median age: KCd = 67 years vs VCd = 69 years
• Median time since diagnosis: KCd = 32.5 months vs VCd = 36.1 months
• High risk disease: KCd = 50.6% vs VCd = 52%
• Early treatment discontinuation: KCd = 21.4% vs VCd = 45.4%
• Response ≥VGPR at 24 weeks: KCd = 40.2% vs VCd = 31.9% OR: 1.48, 90% CI: (0.95, 2.31)
• MRD negative at 24 weeks: KCd = 16.4% vs VCd = 12.5%
• Overall response rate (ORR): OR: 2.72, 90% CI: (1.62, 4.55) p = 0.0014
• High risk disease ≥VGPR: KCd = 35.7% vs VCd = 17.2%
• Standard risk disease ≥VGPR: KCd = 30.3% vd VCd 37.5%
• Adverse events (AE)
  • Neuropathy: KCd = 21.4% vs VCd = 56.3%
  • ≥G3 neuropathy or ≥G2 with pain: KCd = 1.5% vs VCd = 19.8%
  • Serious cardiac: KCd = 4.2% vs VCd = 1.4%
  • Serious renal: KCd = 3.5% vs VCd = 5.4%
  • Serious GI: KCd = 7.7% vs VCd = 5.4%
  • Serious infections: KCd = 51.4% vs VCd = 47.3%

KCd was non-inferior to VCd therapy in terms of VGPR and was superior to VCd in ORR.  The toxicity profile was improved compared to VCd, which led to less early treatment discontinuation, and better tolerability in the KCd group. The adverse event profile was markedly different regarding the level of neuropathy seen in the VCd group. Additional studies should explore the role of extended treatment duration of carfilzomib and comparison of PFS in both groups.