ASH 2018 | Daratumumab triplet regimen as a frontline treatment for multiple myeloma patients non-eligible for ASCT: interim results of the MAIA trial

The 60th American Society of Hematology (ASH) Annual Meeting was held in San Diego, California, from 1–4 December 2018. On Tuesday 4 December 2018, the Late-Breaking Abstracts (LBA) Session took place, during which, Thierry Facon, from the University Hospital of Lille, Lille, France, presented the pre-specified interim analysis of the MAIA clinical trial.

The MAIA study is an international, phase III clinical trial, which examines the efficacy of frontline treatment with the triplet combination of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus (vs) lenalidomide and dexamethasone (Rd) in patients with newly diagnosed multiple myeloma (NDMM) non-eligible for an autologous stem cell transplant (ASCT). Participants were randomized 1:1 to the two treatment arms.

The primary endpoint was progression-free survival (PFS). Key secondary endpoints included: complete response (CR) or better (≥ CR), very good partial response or better (≥ VGPR), minimal residual disease (MRD) negativity rate, overall response rate (ORR), overall survival, and safety. Patients were treated until disease progression (DP) or unacceptable toxicity.

Data are presented as D-Rd vs Rd.

Study Design:

• Number of patients = 368 vs 369
• Age = 73 (range, 45–90); 44% of patients ≥ 75 years
• Gender = 52% male
• Race = 92% white
• International Staging System (ISS) stage: ISS I = 27%; ISS II = 43%; ISS III = 29%
• High-risk cytogenetics [t(4;14); t(4;16); del17p] = 14%
• Treatment: 28-day cycles
  • Lenalidomide: 25 mg orally on days 1–21, until DP
  • Dexamethasone: 40 mg orally on days 1, 8, 15, and 22, until DP; dose was adjusted to 20 mg in patients > 75 years or with bone mass index (BMI) < 18.5
  • Daratumumab: 16 mg/kg intravenously (IV) once a week for cycles 1–2 (QW); once every two weeks for cycles 3–6 (Q2W); once every four weeks thereafter (Q4W), until DP
• Duration of study treatment = 25.3 months (range, 0.1–40.4) vs3 months (range, 0.03–40.6)
• Total number of cycles received = 27 (range, 1–44) vs 22 (range, 1–43)
• MRD sensitivity = 10^-5sensitivity using clonoSEQ, version 2.0

Key Data:

• Data as of 24 September 2018
• Median follow-up = 28 months (range, 0.0–41.4)
• PFS (median) = Not reached vs 31.9 months (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.43–0.73, P < 0.0001); 44% reduction in the risk of progression or death in patients treated with D-Rd
• ≥ CR = 48% vs 25% (odds ratio [OR], 2.75; 95% CI, 2.01–76, P < 0.0001) (sCR = 30% vs 12%; CR = 17% vs 12%)
• ≥ VGPR = 79% vs 53% (OR, 3.4; 95% CI, 2.45–72, P < 0.0001)
• MRD negativity rate = 24% vs 7%, P < 0.0001
• Patients who discontinued treatment = 32% vs 57%
• Main reasons for discontinuation:
  • Progressive disease = 15% vs 24%
  • Adverse events (AEs) = 7% vs 16%
  • Death = 6% vs 4%
• Deaths = 17% vs 21% (HR, 0.78; 95% CI, 0.56–1.1)
• Infusion-related reaction rates = 41%; grade 3/4 = 3%
• Main treatment emergent AEs (TEAE), grade 3/4:
  • Neutropenia= 50% vs 35%
  • Anemia = 12% vs 20%
  • Lymphopenia = 15% vs 11%
  • Pneumonia = 14% vs 8%
• Incidence of second primary malignancy = 3% vs 4%
• TEAEs with outcome of death = 7% vs 6%

Conclusions

The interim results of the MAIA trial show that the addition of daratumumab in the combination treatment of lenalidomide and dexamethasone reduces the risk of disease progression or death by 44% in patients with NDMM non-eligible for an ASCT. The triplet regimen led to significantly deeper responses and a three-fold higher MRD negativity rate. The safety profile of daratumumab is acceptable and similar to that already described in the POLLUX and ALCYONE trials.

References

Facon T. et al. Phase 3 Randomized Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Ineligible for Transplant (MAIA). 2018 Dec 4; LBA #2: ASH 60th Annual Meeting and Exposition, San Diego, CA.