Comparative Efficacy of Acalabrutinib in Frontline Treatment of Chronic Lymphocytic Leukemia: A Systematic Review and Network Meta-analysis

We identified 3 other network meta-analysis that assessed the relative efficacy of frontline Chronic lymphocytic leukemia treatments in fludarabine-ineligible patients.27e29 Of these, only Xu et al27 included a targeted agent, ibrutinib, among the treatments for comparison

Matthew S. Davids; Catherine Waweru; Pauline Le Nouveau; Amie Padhiar; Gautamjeet Singh; Sarang Abhyankar; Veronique Leblond

2020

Scholarcy highlights

  • Chronic lymphocytic leukemia is the most common adult leukemia in Western countries. The annual incidence is 4.2e4.9 per 100,000 and increases markedly with age, with a median age at diagnosis of 70e72 years. In recent years, fludarabine-based therapy has been standard of care for frontline treatment in suitably fit patients. a majority of patients with CLL are considered ineligible for fludarabine-based treatment based on age and/or comorbidities
  • In the form of a Bruton tyrosine kinase inhibitor, ibrutinib, and a B-cell lymphoma-2 protein inhibitor, venetoclax, in combination with obinutuzumab have shown superior efficacy compared with chlorambucil monotherapy, chlorambucil + obinutuzumab, and bendamustine + rituximab in frontline CLL; these therapies are rapidly changing the CLL treatment landscape.4e7
  • progression-free survival and overall survival surface under the cumulative ranking area values for the remaining comparators are provided in Table S12 and Table S13, with all pairwise comparisons given in Table S14 and Table S15. To our knowledge, this analysis is the first to indirectly compare the efficacy of acalabrutinib with frontline CLL treatments, including targeted therapies, in fludarabine-ineligible patients. Analysis of both evidence networks showed that acalabrutinib, as a monotherapy and in combination with obinutuzumab, was associated with a significant improvement in PFS compared with bendamustine + rituximab, chlorambucil-based therapies, and alemtuzumab
  • We identified 3 other network meta-analysis that assessed the relative efficacy of frontline CLL treatments in fludarabine-ineligible patients.27e29 Of these, only Xu et al included a targeted agent, ibrutinib, among the treatments for comparison
  • Acalabrutinib, as monotherapy and in combination with obinutuzumab, showed favorable PFS and OS compared with frontline therapies of CLL in fludarabine-ineligible patients
  • Alemtuzumab was excluded from the OS analysis while an hazard ratios for OS was imputed for ibrutinib versus chlorambucil + obinutuzumab using the OS HR of acalabrutinib monotherapy from ELEVATE-TN on the premise that both treatments belong to the same drug class
  • Our NMAs provide useful insights into the relative efficacy of acalabrutinib compared with other frontline treatments of CLL, the results cannot be considered confirmatory, and head-to-head randomized trials are needed, especially to compare the efficacy of acalabrutinib versus other targeted agents
  • The ongoing ELEVATE-RR trial, for example, will provide important comparative data for acalabrutinib versus ibrutinib, albeit in patients with relapsed/refractory CLL

Need more features? Save interactive summary cards to your Scholarcy Library.