Early initiation of Bruton’s tyrosine kinase inhibitor zanubrutinib in patients with chronic lymphocytic leukemia (CLL), especially in treatment-naïve patients and those who have received one prior therapy, is associated with higher overall responses and increased durability of treatment benefit, according to a study presented by Wei Xu, MD, of the Jiangsu Province Hospital, at the 62nd American Society of Hematology Annual Meeting & Exposition.
In the study, Dr. Xu and colleagues examined pooled data from two phase I and one phase II studies that investigated zanubrutinib monotherapy in patients with CLL and small lymphocytic leukemia.
Efficacy and safety of zanubrutinib were compared between 19 treatment-naïve patients and 31 patients with relapsed/refractory (R/R) disease. Additionally, the investigators compared 93 patients with one prior therapy versus 99 patients with two or more prior therapy lines in the R/R setting.
The efficacy outcomes included complete response rate (CRR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Median follow-up for the treatment-naïve and R/R groups were 31.3 and 20.9 months, respectively. In the R/R group, approximately 54.4% of patients had one prior line of therapy, 18.8% had two, and 26.8% had more than two prior lines of therapy.
Compared with the R/R group, the ORR was significantly higher in the treatment-naïve group (92.1% vs. 100%, respectively; P<0.001). The PFS was superior in treatment-naïve patients compared with the R/R group, but this did not reach statistical significance (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.10-1.09; P=0.13).
The 24-month PFS rate was also proportionally higher in the treatment-naïve group relative to the patients with R/R disease (100% vs. 79.1%). No difference was found between the two groups in terms of OS and safety.
Patients treated with only one prior therapy had a numerically higher ORR compared with patients with two prior therapies (97.0% vs. 88.3%; P=0.05). No difference was found between the two groups in regard to CRR (9.8% vs. 8.4%; P=0.75). However, patients who had received only one prior therapy line had a significantly longer PFS (HR, 0.15; 95% CI, 0.05-0.45; P<0.001) and grater 24-month PFS (94.6% and 75.3%).