IMW 2019 | ELOQUENT-2: Final overall survival results

During the XVII International Myeloma Workshop (IMW) in Boston, US, Professor (Prof.) Meletios Dimopoulos presented the final overall survival (OS) results from the phase III ELOQUENT-2 study.¹

• ELOQUENT-2 was an international, open-label, randomized trial (NCT01239797) comparing elotuzumab (E), lenalidomide (R) and dexamethasone (d, ERd, n= 321) to Rd alone (n= 325)
• Patients had relapsed/refractory multiple myeloma (RRMM) following one to three prior lines of therapy
• Patients were stratified by β2 microglobulin level, number of prior lines of therapy, and prior exposure to immunomodulatory drugs
• Dosing schedule:
  • Intravenous E: 10mg/kg, weekly in cycles one and two, and every other week from cycle three onwards
  • Oral R: 25mg, on days 1­-21
  • Oral d: 40mg, weekly
• Treatment continued until disease progression (PD), unacceptable toxicity or withdrawal of consent
• Endpoints:
  • The co-primary endpoints were Independent Review Committee (IRC)-assessed progression-free survival (PFS) and overall response rate (ORR)
  • The secondary endpoint was OS
  • Safety was an exploratory endpoint

The co-primary endpoint results were previously reported by Sagar Lonial, Meletios Dimopoulos, and colleagues in the New England Journal of Medicine in 2015²

• One-year PFS (ERd vs Rd): 68% vs 57%
• Two-year PFS: (ERd vs Rd): 41% vs 27%
• Median PFS: 19.4 vs 14.9 months
• ORR (ERd vs Rd): 79% vs 66%
• In the intention to treat (ITT) population, ERd gave a 32% reduction in the risk of PD

Read the full report of the primary endpoint analysis on the MM Hub here

Final OS analysis¹

At a data cutoff of 3^rd October 2018, 437 deaths had occurred, with 10% of patients remaining on treatment in the ERd arm compared to 4% in the Rd arm (Table 1). The two-sided alpha value for final OS analysis was determined to be 0.046.

Table 1. Treatment adherence and reason for discontinuations

• The hazard ratio (HR) for ERd vs Rd was 0.82 (95.4% CI, 0.68-1.00, p= 0.0408)
  • ERd gave a 18% reduction in the risk of death compared to Rd alone and prolonged median OS by 8.7 months (Table 2)
  • The p-value of 0.0408 was less than the alpha value of 0.046
  • Therefore, ERd gave a statistically significant and clinically meaningful benefit in OS compared to Rd
• Predefined subgroup analysis showed a consistent benefit of ERd across most patient subsets
• Subsequent therapy given to:
  • ERd group: 60% of patients
  • Rd: 66% of patients

Table 2. Final OS analysis at a minimum follow-up of 71 months

• Less deaths occurred in the ERd arm (Table 3)
  • Deaths (ERd vs Rd): 67% vs 71%
• The safety analysis was consistent with the primary analysis:
  • In total, grade 3-4 serious AEs (ERd vs Rd): 53% vs 40% (Table 4)
  • Grade 3-4 AEs leading to discontinuation (ERd vs Rd): 21% vs 20%
  • Secondary primary malignancy of any grade (ERd vs Rd): 12% vs 9%
  • Infusion reactions in ERd arm: 11%
    • Most (9%) were grade 1-2

Table 3. Summary of deaths

Table 4. Most common grade 3-4 AEs occurring in >2% of patients

Conclusion

Prof. Dimopoulos and colleagues concluded that ERd provided an 18% reduction in the risk of death compared to Rd alone in patients with RRMM who received between one and three prior lines of therapy, at a minimum follow-up of five years with a consistent safety profile across the five-years.