EHA 2018 | Results from the phase III trial of ibrutinib/rituximab versus placebo/rituximab in WM

On Saturday 16^th June an oral abstract session took place at the 23^rd Congress of the European Hematology Association (EHA). Abstract S852 was presented by Meletios Dimopoulos, University of Athens School of Medicine, Athens, Greece, on the results of the phase III randomized trial of ibrutinib/rituximab versus placebo/rituximab in patients with Waldenström’s macroglobulinemia (WM).

Study Overview

• Patients with WM were randomized 1:1 to receive either ibrutinib plus rituximab (ibrutinib-RTX) (n = 75) or placebo plus rituximab (placebo-RTX) (n = 75)
  • Arm A = oral ibrutinib 420mg once daily and RTX 375mg/m² IV
  • Arm B = placebo and RTX 375mg/m² IV
• The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were response rate, time-to-next-treatment (TTNT), sustained hematologic improvement, overall survival (OS) and safety

Key Findings

• At a median follow-up of 26.5 months, the 30-month PFS rate was 82% for (ibrutinib-RTX) and 28% for (placebo-RTX). This improvement in PFS with (ibrutinib-RTX) was also consistent across subgroups:
  • The 24-month PFS rate for treatment-naïve patients by an independent review committee (IRC) was 84% for (ibrutinib-RTX) and 59% for (placebo-RTX)
  • The 30-month PFS rate for relapsed patients by IRC was 80% for (ibrutinib-RTX) and 22% for (placebo-RTX)
• Higher response rates were seen in patients with (ibrutinib-RTX) overall and also in patients with genetic subtypes; MYD88^L265P/CXCR4^WT, MYD88^L265P/CXCR4^WHIM and MYD88^WT/CXCR4^WT
• The decrease in median IgM was more rapid in patients treated with (ibrutinib-RTX) with IgM ≥50 g/L at baseline
• The rate of sustained hemoglobin improvement was significantly higher in patients with (ibrutinib-RTX) vs (placebo-RTX)
  • All patients: 73% vs 41%, rate ratio (95% CI, 1.774 (1.311–2.400), P < 0.0001
  • Baseline hemoglobin ≤11 g/dL: 95% vs 56%, rate ratio (95% CI, 1.705 (1.322–2.197)), P < 0.0001
• The 30-month OS rate was 94% for (ibrutinib-RTX) and 92% for (placebo-RTX)
• The most frequent adverse events (AEs) Grade ≥3 for (ibrutinib-RTX) vs (placebo-RTX):
  • Anemia = 11% vs 17%
  • Hypertension = 13% vs 4%
  • Atrial fibrillation = 12% vs 1%
  • Infusion-related reactions = 1% vs 16%
• There were no unexpected toxicities and 3 Grade 5 AEs occurred on the (placebo-RTX) arm due to intracranial hemorrhage, nervous system disorder and not specified)

Dr Dimopoulos concluded that there were significant improvements in PFS for all WM patients treated with ibrutnib-RTX vs placebo-RTX regardless of prognostic or genotypic factors.