Waldenström macroglobulinemia: Six-year follow-up of phase II trial into front-line BDR in the treatment of newly diagnosed patients

In November 2016, Maria Gavriatopoulou from the National and Kapodistrian University of Athens School of Medicine, Greece, and colleagues published in Blood the results of the six-year follow-up of a multi-center phase II study into the efficacy of chemotherapy-free bortezomib, dexamethasone, and rituximab (BDR) in newly diagnosed WM patients. The study enrolled 59 patients over 10 centers in Europe.

The BDR treatment regimen was 23 weeks long; the first cycle was 21 days with bortezomib IV 1.3mg/m² on days 1, 4, 8, and 11. Bortezomib was then administered weekly for a further four 35-day cycles at 1.6mg/m². On cycles 2 and 5, IV dexamethasone and IV rituximab were also delivered at 40mg and 375mg/m² doses, respectively. 

Highlights:

• Majority of patients recruited were intermediate (40%) or high (45.5%) according to IPSSWM
• ITT analysis:
  • 85% responded with 3% CR, 7% VGPR, 58% PR, 17% MR
  • Major response rate (PR + VGPR + CR) of 68%
• Median PFS: 43 months (with 17% in remission after a median of 90 months)
• 7-year PFS and 7-year OS by risk:
  • Low IPSSWM = 62.5% and 87.5%
  • Intermediate IPSSWM = 42% and 68.2%
  • High IPSSWM = 15% and 48%
• 7-year overall OS = 66%
• Peripheral neuropathy in 46% patients, but this resolved completely or to grade I

The authors concluded by stating that toxicity was mild and that BDR was an active chemotherapy-free treatment, which was shown to result in durable responses over a 6 year follow-up period.