ASH 2017 | Updated data from the POLLUX trial

The MM Hub team have been in Atlanta for the 59th ASH Annual Meeting and Exposition, from 9-12 December 2017. On Monday 11 December, an oral abstract session was held entitled: Session: 653. Myeloma: Therapy, excluding Transplantation I. The first talk in the series was presented by Meletios A. Dimopoulos from the National and Kapodistrian University of Athens, Athens, Greece who presented updated data from the POLLUX trial on behalf of his colleagues and the large team of collaborators. The presented abstract was entitled: Abstract 739: Daratumumab, Lenalidomide, and Dexamethasone (DRd) Versus Lenalidomide and Dexamethasone (Rd) in Relapsed or Refractory Multiple Myeloma (RRMM): Updated Efficacy and Safety Analysis of Pollux.

In the POLLUX study, Relapsed and Refractory Multiple Myeloma (RRMM) patients were randomized to receive either daratumumab, lenalidomide and dexamethasone (DRd) or lenalidomide and dexamethasone (Rd). To see details of the trial set-up, see previously published MM Hub article. Daratumumab was the first humanized anti-CD38 and has both direct and indirect modes of action. Direct actions occur via complement mediated cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and apoptosis via antibody crosslinking, and may contribute to a rapid response, whilst indirect immunomodulatory action may contribute to deep and durable responses. Daratumumab is currently approved in some countries as both a monotherapy and as a combination therapy with other regimens, for the treatment of RRMM patients. This article is based on data presented at the live session and therefore may supersede information in the pre-published ASH Abstract.

Key Data:

• Reduction in risk of progression/death for DRd vs Rd = 56% 
• 30-month PFS^b: DRd = Median not reached; Rd = median 17.5 months; HR = 0.44; (95% CI, 0.34-0.55); P<0.0001
• DRd (n= 281) and DRd (n= 276) for ORR analysis; data given as DRd vs Rd:
• ORR at a median follow-up of 32 months (range, 0-40):
  • ORR = 93% vs 76% (P < 0.0001); sCR = 28% vs 9%; CR = 27% vs 14%; VGPR = 26% vs 26%; PR = 13% vs 28%
• Significantly higher (> 3 fold) MRD-negative Rates^a for DRd vs Rd: 10^-4 = 36% vs 9%, 10^-5 = 27% vs 5%, 10^-6 = 6% vs 0.4%
• Deeper responses were more common on DRd and were associated with longer PFS; MRD negativity was also associated with longer PFS
• MRD negativity occurs more rapidly with DRd and increase over time
• More than half of DRd patients have not started subsequent therapy:
  • Time to next therapy (TNT) = DRd = median not reached and Rd = median 22.,3 months
  • HR = 0.37 (95% CI, 0.29-0.48) P < 0.0001
• DRd does not negatively impact outcomes of subsequent therapy:
  • PFS with subsequent line of therapy (PFS2) = 73% vs 58%
  • DRd = median not reached and Rd = median 32.3 months
  • HR = 0.51; 95% CI 0.38-0.67 P < 0.0001

• Safety:
  • Median treatment duration:30.4 vs 16 months
  • Discontinuation due to AEs: 13% in both arms
  • Rate of grade 3/4 infections: 39% vs 26%
  • Rate of secondary primary malignancies (SPMs): 7% both groups
  • Neutropenia: All grades = 62% vs 47% and 54% vs 41%

The conclusions as stated in the presentation were:

• DRd continues to significantly improve PFS with longer follow-up
• DRd induces deep and durable responses
• More patients receiving DRd achieved MRD negativity vs Rd
• MRD negativity occurs more rapidly with DRd and increases over time
• DRd does not negatively impact outcomes of subsequent therapy
• Safety profile remains unchanged with longer follow-up

Therefore, the updated findings continue to support the use of DRd in patients with RRMM.

To listen to Professor Dimopoulos talking to the MM Hub about this trial, listen here.