Next-generation BTKis demonstrate superior efficacy and safety to ibrutinib/ibrutinib in real-world settings

Real-world data presented at the 2024 American Society of Clinical Oncology Annual Meeting shows that next-generation Bruton's tyrosine kinase inhibitors (BTKis) achieve promising results compared to their first-generation predecessors.

Retrospective observational data from more than 3,000 patients with chronic lymphocytic leukemia (CLL) or small cell leukemia (SLL) treated with BTKi, providing an additional 5 months of follow-up to the previous analysis. Patients were treated with one of two next-generation BTKis, zanubrutinib (Brukinsa; zanubrutinib) or acalabrutinib (Calquence; acalabrutinib), or first-generation ibrutinib/ibrutinib (Ibrutinib; Imbruvica).

In the study, the majority of patients (92%) received first-line (1L) therapy. Of note, the sample size for zanubrutinib was smaller than that for other BTKis, with 7.2% of patients receiving zanubrutinib, 49.3% of patients receiving ibrutinib, and 43.4% of patients receiving acalabrutinib. A similar processing pattern is observed in the second row and beyond. After 9 months of treatment, zanubrutinib had the lowest cardiovascular adverse effects (8.5%), but acalabrutinib also had lower adverse effects (9.4%) than ibrutinib (14.6%), which is consistent with previous data showing a more favorable safety profile of second-generation BTKis. With longer follow-up, a trend toward favorable cardiovascular safety with zanubrutinib was observed.

The median follow-up time was zanubrutinib was 6 months, acalabrutinib was 14.2 months, and ibrutinib was 20.5 months. Among patients receiving ibrutinib 1L, 12.7% switched to zanubrutinib or akrabrutinib. Time to discontinuation was shortest with ibrutinib (median, 13.7 months; 95% CI, 12.2-16), and similar with acalabrutinib (19.2 months; 95% CI, 15.1-25.3) and zanubrutinib (19.3 months, 95% CI, 14.1-not reached).

atOf the 203 patients who received zanubrutinib, the median time to next treatment regimen (TTNT) was not reached (95% CI, 16.7 not reached), and these patients had the highest probability of remaining on 1L therapy at 1 year (75%). Median TTNT was 35.8 months (95% CI, 29.8-not reached) among 1223 patients who received acalabrutinib and 30.2 months (95% CI, 26.2-35.5) among 1389 patients who received ibrutinib. The probability of continuing to receive 1L treatment was 66.3% for patients who received aclarutinib and 67.3% for patients who received ibrutinib.

As the researchers noted that further studies are needed to explore and validate the favorable outcomes of zanubrutinib compared with acalabrutinib, additional data were presented suggesting improved survival with zanubrutinib and other next-generation BTKis. A network meta-analysis from 3 randomized controlled trials (ALPINE, ELEVATE-RR, and ASCEND) showed that in patients with high-risk disease, zanubrutinib had a statistically significant improvement in PFS compared with acalabrutinib, and there was a trend toward improved overall survival, overall response, and complete response.