Zanubrutinib and Venetoclax Combination Is Well-Tolerated, Effective as First-Line Therapy

According to preliminary data from a nonrandomized arm of the SEQUOIA trial, 97% of treatment-naïve patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) and the high-risk genomic abnormality del17p responded to treatment with zanubrutinib and venetoclax.

Lead author Alessandra Tedeschi, MD, from the ASST Grande Ospedale Metropolitano Niguarda in Milan, Italy, shared these findings at the 2021 American Society of Hematology Annual Meeting. He reported that no new safety concerns were identified, and no tumor lysis syndrome (TLS) events occurred among the cohort’s patients during a median follow-up of 9.7 months.

Thirty-five patients were enrolled and treated with zanubrutinib (160 mg twice a day) for 3 months followed by a combination of zanubrutinib and venetoclax (400 mg once a day after a ramp-up cycle) for 12-24 cycles. Treatment continued until patients experienced progressive disease (PD), unacceptable toxicity, or undetectable measurable residual disease (MRD). CLL and SLL responses were assessed by an investigator, and bone marrow exams were required to confirm a suspected complete response (CR).

Among the cohort, 94.3% had CLL and high-risk characteristics including Binet stage C, bulky disease ≥5 cm, unmutated immunoglobulin heavy chain variable locus, elevated β2-microglobulin, and a median del17p frequency of 81.5%.

At data cutoff, adverse events (AEs) were reported in 33 patients, 4 of which were serious AEs. The most commonly reported AEs included diarrhea, neutropenia, fatigue, nausea, and petechiae. Thirteen patients had grade ≥3 AEs, most frequently neutropenia (n, 4) and diarrhea (n, 2). No TLS AEs were reported, despite medium- and high-risk TLS categorizations in 22 and 12 patients at baseline, respectively.

The overall response rate was 96.8% (n, 30/31) among the patients who reached the initial efficacy assessment at 3 months post-zanubrutinib initiation. The only non-responding patient reported PD after having an initial partial response while on combination therapy.

The safety data from the ongoing study supports that the zanubrutinib and venetoclax combination was generally well tolerated, even in the high-risk patient population. Dr. Tedeschi noted that enrollment in the SEQUOIA trial is ongoing.

Disclosures: This research was supported by BeiGene. Study authors report financial relationships with BeiGene, the manufacturer of zanubrutinib.

Reference

Tedeschi A, Ferrant E, Flinn IW, et al. Zanubrutinib in combination with venetoclax for patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with del(17p): early results from Arm D of the SEQUOIA (BGB-3111-304) trial. Abstract #67. Presented at the 2021 American Society of Hematology Annual Meeting, December 11-14, 2021.