Zanubrutinib More Effective in CLL/SLL When Used Earlier

Zanubrutinib has been shown to be an effective treatment in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). An analysis presented at the 62nd ASH Annual Meeting & Exposition evaluated how the number of previous lines of therapy affected zanubrutinib outcomes and found that patients with fewer prior lines of therapy had better outcomes.

The pooled analysis included patients with CLL/SLL who were treated with zanubrutinib monotherapy from two phase I studies with a median follow-up of 29.2 months and 21.1 months, respectively, and one phase II study with a median follow-up of 15.1 months.

Efficacy and safety outcomes were compared between treatment-naïve (TN) and relapsed/refractory (R/R) patients. Comparisons were also made between R/R patients with one prior therapy versus two or more prior therapies. The researchers employed entropy balancing to create a weighted sample and balance baseline covariates between the groups when comparing outcomes, which included complete response rate (CRR), overall response rate (ORR; defined as the achievement of CR or complete remission with incomplete count recovery, partial response [PR], nodular PR, PR with lymphocytosis), progression-free survival (PFS), and overall survival (OS).

Data were available for 19 TN patients, 93 patients with one prior therapy, and 99 patients with two or more prior therapies. Seven patients with missing baseline covariates were excluded from the analysis.

The effective sample sizes after weighing were 19 in the TN group and 31 in the R/R groups; median follow-up was 31.3 months and 20.9 months, respectively. In the R/R group, the numbers of prior lines of therapy were one (54.4%), two (18.8%), and more than two (26.8%). The TN group, compared with the R/R group, had higher ORR (100.0% vs. 92.1%; P<0.001), CRR (21.05% vs. 6.70%; P=0.09), and PFS (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.10-1.09; P=0.13). At 24 months, the PFS rate was 100% in the TN group and 79.1% in the R/R group. OS and safety profile were similar between the groups.

The effective sample sizes after weighting were 77 in the one prior therapy and 85 in the two or more prior therapies groups; median follow-up was 17.1 months and 15.8 months, respectively. In the two or more prior lines of therapy group, the numbers of prior lines of therapy were two (56.5%), three (20.6%), and three or more (22.9%). The one prior therapy group had higher ORR than the two or more prior therapies group (97.0% vs. 88.3%; P=0.05), but CRR did not largely differ (9.8% vs. 8.4%; P=0.75). The one prior therapy group had significantly longer PFS than the two or more prior therapies group (HR, 0.15; 95% CI, 0.05-0.45; P<0.001). At 24 months, the PFS rate was 94.6% in the one prior therapy group and 75.3% in the two or more prior therapies group. OS and safety profile were similar between the groups.