Acalabrutinib with or without obinutuzumab significantly improves progression-free survival (PFS) compared with obinutuzumab-chlorambucil for treatment-naive chronic lymphocytic leukaemia (CLL), according to a study published in the Lancet.
The finding is from the global, phase 3, multicentre, open-label ELEVATE TN trial. Eligibility criteria for the trial was untreated CLL, age ≥65 years, or 18-64 years with Cockcroft-Gault creatinine clearance of 30-69 mL/min or Cumulative Illness Rating Scale for Geriatrics score >6. Additional criteria included an ECOG performance score of ≤2 and adequate haematologic, hepatic, and renal function.
A total of 675 patients were recruited, of whom 535 patients were randomly assigned to receive acalabrutinib-obinutuzumab (n=179), acalabrutinib monotherapy (n=179), or obinutuzumab-chlorambucil (n=177).
At median follow-up of 28.3 months, median PFS was longer with acalabrutinib-obinutuzumab and acalabrutinib monotherapy, compared with obinutuzumab-chlorambucil (median not reached with acalabrutinib and obinutuzumab vs 22.6 months with obinutuzumab, hazard ratio [HR] 0.1; 95% CI 0.06-0.17; P<0.0001; and not reached with acalabrutinib monotherapy vs 22.6 months with obinutuzumab, HR 0.20; 95% CI 0.13-0.3, P<0.0001).
Estimated two-year PFS was 93% with acalabrutinib-obinutuzumab, 87% with acalabrutinib monotherapy, and 47% with obinutuzumab-chlorambucil.
The most common grade ≥3 adverse event was neutropenia (30% in the acalabrutinib-obinutuzumab group, 9% in the acalabrutinib group, and 41% of the obinutuzumab-chlorambucil group).
Grade ≥3 infections occurred in 21%, 14%, and 8%, respectively. Deaths occurred in 4%, 7%, and 9%, respectively.
Commenting on the findings, the authors said acalabrutinib provides a chemotherapy-free treatment option with an acceptable side-effect profile that was consistent with previous studies.
