An indirect comparison of acalabrutinib with and without obinutuzumab vs zanubrutinib in treatment-naive CLL

Blood Adv. 2024 Jun 11;8(11):2861-2869. doi: 10.1182/bloodadvances.2023012142.

Abstract

The efficacy and safety of acalabrutinib plus obinutuzumab and acalabrutinib monotherapy vs zanubrutinib in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma without del(17p) were compared using an unanchored matching-adjusted indirect comparison. Individual patient-level data from ELEVATE-TN (acalabrutinib plus obinutuzumab, n = 162; acalabrutinib monotherapy, n = 163) were weighted to match published aggregate baseline data from SEQUOIA cohort 1, which excluded patients with del(17p) (zanubrutinib, n = 241), using variables that were prognostic/predictive of investigator-assessed progression-free survival (INV-PFS) in an exploratory Cox regression analysis of ELEVATE-TN. After matching, INV-PFS was longer with acalabrutinib plus obinutuzumab (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.23-0.74) and comparable with acalabrutinib monotherapy (HR, 0.91; 95% CI, 0.53-1.56) vs zanubrutinib. Acalabrutinib monotherapy had significantly lower odds of any grade hypertension vs zanubrutinib (odds ratio [OR], 0.44; 95% CI, 0.20-0.99), whereas acalabrutinib plus obinutuzumab had significantly higher odds of neutropenia (OR, 2.19; 95% CI, 1.33-3.60) and arthralgia (OR, 2.33; 95% CI, 1.37-3.96) vs zanubrutinib. No other significant differences in safety were observed. In summary, acalabrutinib plus obinutuzumab had longer INV-PFS with increased odds of neutropenia and arthralgia than zanubrutinib, whereas acalabrutinib monotherapy had similar INV-PFS with lower odds of any grade hypertension. These trials were registered at www.ClinicalTrials.gov as #NCT02475681 and #NCT03336333.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Benzamides* / administration & dosage
  • Benzamides* / adverse effects
  • Benzamides* / therapeutic use
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell* / mortality
  • Male
  • Middle Aged
  • Piperidines
  • Pyrazines* / administration & dosage
  • Pyrazines* / adverse effects
  • Pyrazines* / therapeutic use
  • Pyrazoles* / administration & dosage
  • Pyrazoles* / adverse effects
  • Pyrazoles* / therapeutic use
  • Pyrimidines* / administration & dosage
  • Pyrimidines* / adverse effects
  • Pyrimidines* / therapeutic use
  • Treatment Outcome

Substances

  • acalabrutinib
  • obinutuzumab
  • Benzamides
  • Antibodies, Monoclonal, Humanized
  • zanubrutinib
  • Pyrazines
  • Pyrimidines
  • Pyrazoles
  • Piperidines

Associated data

  • ClinicalTrials.gov/NCT03336333
  • ClinicalTrials.gov/NCT02475681