Updated results from the POLLUX clinical trial

Daratumumab (dara) is a humanized monoclonal antibody that binds to CD38, a molecule found on the cell surface of the majority of multiple myeloma (MM) cells.  Dara has been approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as a treatment for patients with relapsed and/or refractory (RR)MM either as a monotherapy or in combination with bortezomib (bor) and lenalidomide (len). In addition, dara has recently been approved by the FDA and EMA as a front-line treatment in combination with bor, melphalan, and prednisone for newly diagnosed (ND)MM patients.

In the POLLUX study, an on-going, phase III, multi-centered clinical trial, RRMM patients were randomized to receive either dara, in combination with len and low-dose dexamethasone (dex), or len with dex. Results from the first interim analysis of this study (13.5 months follow-up time) showed a significant reduction in disease progression or death in the dara/len/dex group compared to the len/dex group¹.

The lead investigator of the POLLUX study, Meletios A. Dimopoulos from the Athens School of Medicine, Athens, Greece, and colleagues, continued to follow up on the PFS results. They also examined PFS among groups of patients with specific characteristics and have evaluated the impact of each treatment on the minimal residual disease (MRD). These updated results were published in Heamatologica in September 2018.

Results are presented as dara/len/dex vs len/dex.

Key Data:

• Total number of patients = 569; 286 vs 283 patients
• Median duration of study treatment = 24.5 months (range, 0–32.7) vs 16.0 months (range, 0.2–32.2)
• Median duration of follow-up = 25.4 months (range, 0–32.7)
• PFS = not reached (NR) vs 17.5 months (hazard ratio [HR] = 0.41; 95% confidence interval [CI], 0.31–0.53, P < 0.0001); 24-month PFS rates = 68.0% vs 40.9%
• Overall response rate (ORR) = 92.9% vs 76.4% (P < 0.0001)
• Stringent Complete response (CR) = 26% vs 8.7%
• Complete response (CR) or better (≥ CR) = 51.2% vs 21% (P < 0.0001)
• Post hoc analysis of PFS and ORR in various subgroups of patients:
  • PFS in patients with one prior line of therapy = NR (n = 149 patients) vs 19.6 months (n = 146 patients) (HR = 0.39; 95% CI, 0.26–0.58, P < 0.0001); 24-month PFS = 70.3% vs 45%
  • PFS in patients with two–three prior lines of therapy = 28.9 months (n = 123 patients) vs 15.7 months (n = 118 patients) (HR = 0.38; 95% CI, 0.26–0.56, P < 0.0001)
  • ORR in patients with one prior line of therapy = 93.2% (n = 147) vs 80.3% (n = 142), P = 0.0003
  • ORR in patients with two–three prior lines of therapy = 95% (n = 120) vs 73.9% (n = 115)
  • PFS in bor refractory patients = 26.1 months (n = 59) vs 11.3 months (n = 58) (HR = 0.46; 95% CI, 0.20–0.47, P = 0.0001); 24-month PFS = 74.3% vs 40.0%
  • ORR in bor refractory patients = 87.7% (n = 57) vs 67.9% (n = 56)
  • PFS in high cytogenetic risk patients = 22.6 months (n = 28) vs 10.2 months (n = 37) (HR = 0.53, 95% CI, 0.25–1.13, P = 0.0921); 24-month PFS rate = 48.1% vs 31.7%
  • PFS in standard risk patients = NR (n = 133) vs 18.5 months (n = 113) (HR = 0.30, 95% CI, 0.25–1.13, P = 0.0921); 24-month PFS rate = 48.1% vs 31.7%
  • ORR in high cytogenetic risk patients = 85.2% (n = 27) vs 66.7% (n = 36), P = 0.0435
  • ORR in standard risk patients = 94.7% (n = 132) vs 82% (n = 111), P = 0.0004
• MRD negativity = 26.2% vs 6.4% (sensitivity threshold = 10^-5, P < 0.000001)
• Deeper responses and higher MRD-negative rates in the dara/len/dex group vs the len/dex group for all subgroups evaluated
• Safety profile = same as previously described
• Health-related quality of life (HRQoL) = no decline with the addition of dara

Conclusions

The current update on the POLLUX study supports previously published results indicating superior PFS and ORR in patients with RRMM treated with dara/len/dex vs len/dex. In addition, the dara/len/dex combination results in a significantly improved MRD negativity compared to that observed in the len/dex group.