ASH 2018 | Results of a phase III study for elderly, intermediate-fit patients with newly diagnosed multiple myeloma

The 60th American Society of Hematology (ASH) Annual Meeting was held in San Diego, California, from 1–4 December 2018. On Sunday 2 December 2018, an oral abstract session was held entitled: Myeloma: Therapy, excluding Transplantation: Novel Targeted Combinations in Myeloma, which focused on updates of clinical trials using novel combination regimens for patients with multiple myeloma (MM).

Alessandra Larocca from the GIMEMA, European Myeloma Network, Italy, presented results of an ongoing phase III clinical trial designed specifically for elderly, intermediate-fit patients with newly diagnosed multiple myeloma (NDMM).¹

This randomized trial compared the effectiveness and safety of lenalidomide and dexamethasone treatment, followed by lenalidomide maintenance (Rd-R) (Arm 1) with continuous lenalidomide and dexamethasone (Rd) treatment (Arm 2). Patients were included in the trial if they had a frailty score equal to one, according to the International Myeloma Working Group (IMWG) criteria.²

The rationale of the trial was based on previous data showing the effectiveness of lenalidomide and dexamethasone (Rd) treatment in elderly patients with NDMM. The primary endpoint was event-free survival (EFS), defined as disease progression or death for any cause, discontinuation of lenalidomide therapy and occurrence of any hematological grade 4 or non-hematological grade 3-4 adverse events (AEs), including second primary malignancies (SPMs).

Data are presented as Rd-R (Arm 1) versus (vs) Rd (Arm 2).

Study Design:

• Key inclusion criteria:
  • IMWG frailty score = 1
  • Patients > 65 and ≤ 80 years unfit and unsuitable for standard treatments
• Key exclusion criteria:
  • Fit (IMWG frailty score = 0) or frail (IMWG frailty score ≥ 2) patients
• Treatment: 28-day cycles
  • Arm 1 = Rd induction for 9 cycles: lenalidomide, 25 mg orally on days 1–21; dexamethasone, 20 mg orally on days 1, 8, 15, and 22; R maintenance: lenalidomide, 10 mg orally on days 1–21 until disease progression (DP) or intolerance
  • Arm 2 = Rd continuous: lenalidomide, 25 mg orally on days 1–21; dexamethasone, 20 mg orally on days 1, 8, 15, and 22 until DP or intolerance

Key Data:

• Number of patients = 101 vs 98
• Age = 75 years (range, 73–77) (48% > 75 years) vs 76 years (range, 74–79) (57% > 75 years)
• International Staging System (ISS) stage: ISS I = 32% vs 38%; ISS II = 48% vs 37%; ISS III = 21% vs 26%
• Cytogenetic abnormalities: High-risk [t(4;14); t(4;16); del17p] = 13% vs 16%
• Median follow-up = 25 months
• Median EFS = 9.3 months vs6 months (HR, 0.72; 95% confidence interval [CI], 0.52–0.99, P = 0.044)
• Early drop-out rate (< 60 days from initiation of treatment) = 9%, mainly due to toxicity
• Response rates:
  • Near complete response or better (≥ nCR) = 19% vs 15%, not significant (ns)
  • Very good partial response or better (≥ VGPR) = 44% vs 35%, ns
  • Partial response or better (≥ PR) = 73% vs 63%, ns
• 20-month progression free-survival = 43% vs 42%, ns
• 20-month overall survival = 84% vs 79%, ns
• AEs, grade 3 or > :
  • Neutropenia = 17% vs 14%
  • Thrombocytopenia = 2% vs 2%
  • At least one non-hematologic AE = 31% vs 39%
  • Central nervous system-related = 0% vs 6%
  • Infections = 9% vs 11%
  • Dermatologic = 3% vs 7%
  • SPM = 2% vs 1%
• Lenalidomide discontinuation due to AEs = 19% vs 23%
• Lenalidomide dose reduction due to AEs = 33% vs 43%

Conclusions

The results of this study show that Rd-R treatment has similar efficacy to Rd treatment for intermediate-fit patients with newly diagnosed multiple myeloma and underlines the need of adjusting the treatment approach to balance efficacy and safety.

References               

1. Larocca A. et al. Efficacy and Feasibility of Dose/Schedule-Adjusted Rd-R Vs. Continuous Rd in Elderly and Intermediate-Fit Newly Diagnosed Multiple Myeloma (NDMM) Patients: RV-MM-PI-0752 Phase III Randomized Study. 2018 Dec 2; Oral Abstract #305: ASH 60th Annual Meeting and Exposition, San Diego, CA.
2. Palumbo A. et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015 Mar 26;125(13):2068-74. DOI: 10.1182/blood-2014-12-615187.