MAIA results confirm superior efficacy of daratumumab with standard-of-care

In patients with newly diagnosed multiple myeloma (MM), daratumumab in combination with standard-of-care (i.e. lenalidomide and dexamethasone) achieved superior outcomes in overall survival (OS), progression-free survival (PFS), and overall response rate compared with standard-of-care alone, as demonstrated by the overall survival results of the phase 3 MAIA trial.

The phase 3 MAIA (NCT02252172), ALCYONE (NCT02195479), and CASSIOPEIA (NCT02541383) studies established the superior PFS of daratumumab with standard-of-care versus standard-of-care alone for patients with newly diagnosed MM [1–3]. ALCYONE also established, for the first time, an OS benefit of a daratumumab-based regimen in newly diagnosed MM without eligibility for autologous stem cell transplantation [4]. In the previous MAIA update, OS data was not yet mature [5]. At the EHA 2021 congress, Prof. Thierry Facon (University of Lille, France) reported the updated efficacy and safety results from a pre-specified interim analysis after a median follow-up of 56.2 months [6].

MAIA is a multicentre, randomised, open-label, active-controlled phase 3 study of daratumumab plus lenalidomide and dexamethasone (D-Rd; n=364) versus lenalidomide and dexamethasone alone (Rd; n=365). Participants were randomised 1:1 and received treatment in cycles of 28 days until disease progression. Primary endpoint was PFS. Secondary endpoints included OS and overall response rate.

Median duration of follow-up was 56.2 months, with 42% of patients in the D-Rd arm and 18% of patients in the Rd arm remaining on treatment. Adverse events led to more patients discontinuing in the Rd-arm (23%) than in the D-Rd arm (13%). No new safety concerns were identified with longer follow-up.

The updated PFS data showed a 60-month PFS rate of 52.5% in D-Rd versus 28.7% in Rd (P<0.0001). Median PFS has not been reached with D-Rd so far and was 34.4 months with Rd. These results provide a new PFS benchmark in patients with newly diagnosed MM who are transplant ineligible. Overall response rate analysis showed that D-Rd induced deeper responses with significantly higher rates of complete response and very good partial response [2]. With >28 months of additional follow-up, responses deepened with continued daratumumab therapy.

D-Rd also demonstrated a significant benefit (P=0.0013) in OS, with a 32% reduction in the risk of death: 60-month OS rate was 66.3% in D-Rd and 53.1% in Rd (see Figure). Subgroup analysis confirmed OS benefit with D-Rd, as it was consistent across patient subgroups.

Figure: Overall survival data from an interim analysis show superior efficacy of D-Rd versus Rd [1]

CI, confidence interval; D-Rd, daratumumab + lenalidomide and dexamethasone; HR, hazard ratio; NR, not reached; OS, overall survival; Rd, lenalidomide and dexamethasone.

In summary, after almost 5 years of follow-up, a significant OS benefit of D-Rd versus Rd was demonstrated in patients with transplant-ineligible, newly diagnosed MM, representing a 32% reduction in the risk of death. The significant PFS benefit of D-Rd was maintained and no new safety concerns were identified with continuous therapy and longer follow-up. Prof. Facon concluded, “These results strongly support upfront D-Rd as new standard-of-care for patients with transplant-ineligible, newly diagnosed MM.”

1. 
   
   1. Mateos MV, et al. N Eng J Med 2018;378(6):518–28.
   2. Facon T, et al. N Eng J Med 2019;380(22):2104–15.
   3. Moreau P, et al. Lancet 2019;394(10192):29–38.
   4. Mateos MV, et al. Lancet 2020;395(10218):132–41.
   5. Kumar SK, et al. Abstract 2276, ASH 2020, 5–8 December.
   6. Facon T, et al. Overall survival results with daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: phase 3 MAIA study. P205-1, EHA 2021 Virtual Congress, 9–17 June.

 

Copyright ©2021 Medicom Medical Publishers



Posted on 5 August 20215 August 2021