Bruton Tyrosine Kinase Inhibitor Zanubrutinib in Patients with CLL and SLL

Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) who have a deleted chromosome 17p13.1 (del[17p]) often respond poorly to standard chemoimmunotherapy. Several new options have emerged as potentially valuable therapies in this high-risk patient group.

The SEQUOIA trial includes a nonrandomized subgroup known as arm C. Arm C included previously untreated patients with del(17p) CLL/SLL. Patients were eligible for this trial if they were either 65 years of age or older, or younger but unsuitable for treatment with FCR (fludarabine, cyclophosphamide, and rituximab), the standard chemotherapy. Zanubrutinib was given at a dose of 160 mg twice daily. Use of long-term anticoagulation was permitted.

In total, 109 patients with confirmed del(17p) were enrolled into arm C. As of August 2019, all patients had received at least 1 dose of zanubrutinib and were included in the safety and efficacy analyses. Their median age was 70 years.

Median follow-up for safety analysis was 10 months. At cutoff, almost all (104 of 109) patients remained on zanubrutinib treatment. The most common side effects included bruises, rash, upper respiratory tract infection, and nausea. Severe side effects were reported in approximately one-third of patients, and included decreased white blood-cell count, anemia, pneumonia, kidney stones, and high blood pressure. One patient died due to pneumonia that occurred 1 week after the last dose of zanubrutinib. To date, atrial fibrillation has not been reported.

After median follow-up of 10 months, all 109 patients were evaluable for efficacy. Of these, 103 patients remained on study treatment. Their overall response rate was 93%. Four patients had disease progression and 1 patient discontinued because of an adverse event; this patient subsequently died of pneumonia.

This is one of the largest groups of previously untreated patients with del(17p) CLL/SLL evaluated in a clinical trial. Researchers concluded that these results suggest that zanubrutinib is active and generally well tolerated in this high-risk patient group.

Abstract 499. ASH 2019.