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Combined analysis of the impact of second-generation BTK inhibitors on patient outcomes

Robert A Redd1, Josie Ford2, Matthew Lei3

  • 1Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.

Leukemia & Lymphoma
|October 6, 2023
PubMed

Insights

Second-generation BTK inhibitors, acalabrutinib and zanubrutinib, show improved safety profiles compared to ibrutinib in B-cell malignancies. These targeted therapies significantly reduce adverse events like atrial fibrillation, bleeding, and infections.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Bruton's tyrosine kinase inhibitors (BTKi) are crucial for treating B-cell malignancies.
  • Ibrutinib, a first-generation BTKi, has demonstrated efficacy but is associated with significant adverse events.
  • Second-generation BTKi, such as acalabrutinib and zanubrutinib, aim to improve safety profiles.

Purpose of the Study:

  • To compare the safety outcomes of second-generation BTKi (acalabrutinib, zanubrutinib) versus ibrutinib in patients with B-cell malignancies.
  • To evaluate the impact of these BTKi on specific adverse events including atrial fibrillation/flutter, hypertension, bleeding, diarrhea, and infections.

Main Methods:

  • A systematic review and meta-analysis of published/presented randomized trials comparing second-generation BTKi with ibrutinib.
  • Reconstruction of individual patient-level, censored time-to-event data for adverse events.
  • Inclusion of data from 1386 patients across the ELEVATE-RR, ALPINE, and ASPEN trials.

Main Results:

  • Acalabrutinib or zanubrutinib were associated with significant reductions in the cumulative event rates of atrial fibrillation/flutter (HR 0.28), bleeding (HR 0.65), diarrhea (HR 0.61), hypertension (HR 0.40), and infections (HR 0.83) compared to ibrutinib.
  • All reductions were statistically significant (p < 0.05), with atrial fibrillation/flutter showing the most pronounced decrease.

Conclusions:

  • Second-generation BTK inhibitors, acalabrutinib and zanubrutinib, exhibit a favorable safety profile in patients with relapsed/refractory B-cell malignancies.
  • These findings support the use of acalabrutinib or zanubrutinib as preferred BTK inhibitors for their approved indications due to improved safety outcomes.
Keywords:
BTK inhibitoracalabrutinibchronic lymphocytic leukemiaibrutinibsmall lymphocytic lymphomazanubrutinib

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