Zanubrutinib wins battle of BTK inhibitors in relapsed or refractory CLL/SLL

Zanubrutinib outperformed ibrutinib with regard to progression-free survival (PFS) in patients with relapsed or refractory chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). Furthermore, zanubrutinib was associated with fewer toxicities than ibrutinib in this population.

The second-generation Bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib was superior to chemo-immunotherapy in newly diagnosed patients with CLL/SLL without del(17p) [1]. At ASH 2022, Prof. Jennifer Brown (Dana Farber Cancer Institute, MA, USA) presented the final PFS data on zanubrutinib in CLL/SLL from the phase 3 ALPINE study (NCT03734016) [2]. This trial randomised 652 patients with relapsed or refractory CLL/SLL 1:1 to zanubrutinib 160 mg twice daily or to ibrutinib 420 mg once daily.

After a median follow-up of 29.6 months, the PFS was significantly longer in participants who were exposed to zanubrutinib than in those who received ibrutinib (HR 0.65; 95% CI 0.49–0.86; P=0.0024; see Figure). The corresponding 2-year PFS rates were 79.5% and 67.3%. Prof. Brown added that this result was consistent in patients with del(17p) and/or TP53-mutated disease (n=150; HR 0.52; 95% CI 0.30–0.88; P=0.134). The 2-year PFS rates for this subgroup of patients were 77.6% and 55.7%. Additionally, fewer patients died in the zanubrutinib group compared with the ibrutinib group (14.7 vs 18.5%; HR 0.76; 95% CI 0.51–1.11), but this did not reach statistical significance.

Figure: Zanubrutinib is significantly superior to ibrutinib regarding PFS [1]



PFS, progression-free survival.

Reprinted from Brown JR, et al. Blood. 2022;140 (Supplement 2):LBA-6. DOI: 10.1182/blood-2022-171538. Copyright 2022, with permission from Elsevier.

According to Prof. Brown, the safety profile of zanubrutinib was more favourable than that of ibrutinib. Serious adverse events (AEs) occurred in 42.0% of participants on zanubrutinib and in 50.0% of participants on ibrutinib. AEs leading to treatment discontinuation were observed in 15.4% of the participants in the zanubrutinib arm and in 22.2% of the participants in the ibrutinib arm. Importantly, a lower rate of serious cardiac AEs was reported for participants receiving zanubrutinib than for those receiving ibrutinib (1.9% vs 7.7%).

The ALPINE study showed the superiority of zanubrutinib over ibrutinib with regard to PFS in patients with relapsed or refractory CLL/SLL. Moreover, this head-to-head comparison revealed a favourable safety profile of zanubrutinib.

1. Tam CS, et al. Lancet Oncol. 2022;23(8):1031–1043.
2. Brown JR, et al. Zanubrutinib Demonstrates Superior Progression-Free Survival (PFS) Compared with Ibrutinib for Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (R/R CLL/SLL): Results from Final Analysis of ALPINE Randomized Phase 3 Study. Late-Breaking Abstract 6, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.

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Posted on 20 February 20236 September 2023