First-line treatments for chronic lymphocytic leukemia: Analysis of 7 trials based on the restricted mean survival time

Int J Clin Pharmacol Ther. 2021 Apr;59(4):322-327. doi: 10.5414/CP203852.

Abstract

Objective: The purpose of this study was to assess the effectiveness of the newest first-line treatments for chronic lymphocytic leukemia (CLL), used alone or in combination, in comparison with standard treatments.

Materials and methods: We selected 15 cohorts of patients published in 7 clinical trials. The restricted mean survival time (RMST) was used for analyzing survival curves, performing the comparisons and ranking the treatments based on their effectiveness. The endpoint was progression-free survival (PFS).

Results: 15 patient cohorts receiving 11 different first-line treatments were studied. Overall, all of the newest treatments had a positive effect on PFS compared with the old standards. As compared with chlorambucil monotherapy, the improvement in PFS resulting from targeted therapies ranged from 5.4 to 7.3 months per patient. Excluding chlorambucil alone or combined with obinutuzumab, the remaining 11 targeted treatments showed nearly identical values of PFS. Numerically but not statistically, ibrutinib plus venetoclax was associated with the longest PFS. Post-hoc pairwise comparisons were calculated to better interpret these results.

Conclusion: Our results provide an updated overview of the efficacy of the newest first-line treatments for CLL. Our findings confirm the good performance of RMST in this type of analyses.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Chlorambucil / therapeutic use
  • Disease-Free Survival
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
  • Pyrazoles / therapeutic use
  • Survival Rate

Substances

  • Pyrazoles
  • Chlorambucil