C057 | SEQUOIA 5-YEAR FOLLOW-UP IN ARM C: FRONTLINE ZANUBRUTINIB MONOTHERAPY IN PATIENTS WITH DEL(17P) AND TREATMENT-NAIVE CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA

BACKGROUND: Zanubrutinib (zanu), a next-generation Bruton tyrosine kinase inhibitor, is approved for CLL/SLL. Initial results from the SEQUOIA study (NCT03336333) demonstrated superior progression-free survival (PFS) by independent review with zanu vs bendamustine + rituximab (arms A and B) in patients (pts) with treatment-naive (TN) CLL/SLL without del(17p) as well as high overall response rate (ORR) and PFS benefit in pts with del(17p) (arm C). Additionally, the 5-y follow-up in arm A demonstrated durable PFS benefit, with estimated 60-mo PFS rate of 76%. Here we report updated results in SEQUOIA arm C, in pts with del(17p), after approximately 5 y of follow-up (data cutoff: Apr 30, 2024). METHODS: Arm C is a nonrandomized cohort of SEQUOIA pts with del(17p) that received zanu monotherapy. Investigator-assessed PFS, overall survival (OS), ORR, and safety/tolerability were evaluated. Adverse events (AEs) were recorded until disease progression or start of next-line therapy. RESULTS: Between Feb 2018 and Mar 2019, 111 TN pts with del(17p) were enrolled to receive zanu; median age was 71 y (range, 42-87 y), 67 (60%) were IGHV unmutated, and 47 (42%) had both del(17p) and TP53 mutation. At median follow-up of 65.8 mo (range, 5-75 mo), median PFS was not reached. The estimated 60-mo PFS rate was 72.2% (62.4%-79.8%) (Figure), or 73.0% (63.3%-80.6%) when adjusted for COVID-19. Median OS was not reached. The estimated 60-mo OS rate was 85.1% (76.9%-90.6%), or 87.0% (79.0%-92.1%) when adjusted for COVID-19. The ORR was 97.3%, and the complete response/complete response with incomplete hematologic recovery rate was 18.2%. Zanu treatment was ongoing in 62.2% of pts. The most common causes for treatment discontinuation were AEs and progressive disease (in 17.1% and 15.3%, respectively). Most common AEs of interest (AEI) included any-grade infection (82%), bleeding (60%) and neutropenia (19%). Grade ≥3 AEI included infection (33%), neutropenia (16%), and hypertension (8%). CONCLUSIONS: With this 5-y follow-up in SEQUOIA, the efficacy of zanu in TN higher-risk pts with del(17p) was maintained, and pts continue to demonstrate PFS benefits consistent with the randomized cohort of pts without del(17p) (arm A). Additionally, with longer-term follow-up, no new safety signals were identified. This update, in the largest cohort of uniformly treated pts with del(17p), suggests that zanu remains a valuable frontline treatment option for patients with or without del(17p) CLL/SLL.