CLL Coverage from Every Angle

EHA2021: ALPINE Trial of Zanubrutinib Versus Ibrutinib in Resistant CLL

By: Joseph Fanelli
Posted: Thursday, June 17, 2021

According to the first interim analysis of the phase III ALPINE study, presented during the European Hematology Association Virtual Congress (EHA2021; Abstract LB1900), treatment with the second generation Bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) resulted in superior outcomes when compared with standard treatment with the first-generation BTK inhibitor ibrutinib. The newer agent was reported to have yielded a superior response rate, improved progression-free survival, and a lower rate of atrial fibrillation or flutter, concluded Wojciech Jurczak, MD, PhD, of the Maria Skłodowska-Curie National Research Institute of Oncology, Krakow, Poland, and colleagues.

“These data confirm that more selective BTK inhibition, with more complete and sustained BTK occupancy, results in improved efficacy and safety outcomes,” the authors concluded.

In the ALPINE study, the authors focused on 415 patients with relapsed or refractory CLL or SLL. The patients were treated with either 160 mg of zanubrutinib twice daily or 420 mg of ibrutinib once daily.

At a median follow-up of 15 months, the authors reported an overall response rate that was significantly higher with zanubrutinib (78.3%) versus ibrutinib (62.5%). Additionally, among patients who received zanubrutinib, the overall response rate was higher when accounting for 11q deletion (83.6%) than without it (69.1%), as well with 17p deletion (83.3% vs. 53.8% for those without it).

The authors noted that the rate of atrial fibrillation or flutter was significantly lower for patients treated with zanubrutinib (2.5%) versus ibrutinib (10.1%). The rates of major bleeding (2.9% vs. 3.9%), adverse events leading to treatment discontinuation (7.8% vs. 13.0%), and death (3.9% vs. 5.8%). were all lower as well for patients who received zanubrutinib compared with ibrutinib. Rates of neutropenia, however, were observed to be higher with zanubrutinib than with ibrutinib (28.4% vs. 21.7%).

Disclosure: For full disclosures of the study authors, visit

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