NCCN recommendation of zanubrutinib as first-line and second-line therapy in chronic lymphocytic leukemia/small lymphocytic lymphoma

On December 3, 2020, the National Comprehensive Cancer Network (NCCN) guidelines were updated, and they recommended zanubrutinib as first-line and second-line therapy for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).¹

The first-line treatment recommendation is for patients with del(17p) and/or TP53 mutations, who have a contraindication to other Bruton’s tyrosine kinase inhibitors.¹ This recommendation was based on results of the phase III SEQUOIA study of zanubrutinib monotherapy in treatment-naïve patients with CLL or SLL and del(17p) (NCT03336333), which were previously reported on the Lymphoma Hub. Updated results were presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.² With a longer follow-up of 21.9 months, the overall response rate was 94.5%, with a complete response/complete response with incomplete bone marrow recovery of 6.4%. The 18-month progression-free survival and overall survival were 90.6% and 95.4%, respectively. Tolerability was similar to that previously reported.²

The second-line treatment recommendation is for patients with/without del(17p) and/or TP53 mutations, who have an intolerance or contraindication to other Bruton’s tyrosine kinase inhibitors.¹ This was based on the results of a phase II trial (NCT03206918), previously reported on Lymphoma Hub, which led to the approval of zanubrutinib in China for patients with CLL/SLL. Results of this trial showed an overall response rate of 84.6%, with a median follow-up of 15.1 months. The 12-month overall survival was 96%, and zanubrutinib was generally well tolerated, with 9% of patients discontinuing treatment because of adverse events. The most commonly reported Grade ≥ 3 adverse events were neutropenia (44%), thrombocytopenia (15.4%), and lung infection/pneumonia (13.2%).³

Currently zanubrutinib is only approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with mantle cell lymphoma.