ZANUBRUTINIB (ZANU) VERSUS BENDAMUSTINE + RITUXIMAB (BR) IN PATIENTS (PTS) WITH TREATMENT‐NAïVE (TN) CLL/SLL: EXTENDED FOLLOW‐UP OF THE SEQUOIA STUDY

Abstract

Introduction: Zanu, a next-generation Bruton tyrosine kinase inhibitor (BTKi), demonstrated superior progression-free survival (PFS) by independent review versus BR in pts with TN CLL/SLL without (w/o) del(17p) in the SEQUOIA study (NCT03336333) at a median follow-up of 26.2 mo; pts with del(17p) treated with zanu in a separate cohort had similar outcomes to pts w/o del(17p). Here, updated efficacy and safety results from the SEQUOIA study after 18 mo of additional follow-up (data cutoff 31 October 2022) are reported. Methods: Patients w/o del(17p) were randomized to zanu or BR. Pts with del(17p) received zanu monotherapy. Investigator-assessed PFS, overall survival (OS), overall response rate, and safety/tolerability were evaluated. Results: A total of 479 pts w/o del(17p) were randomized (zanu: n = 241; BR: n = 238). At a median follow-up of 43.7 mo, median PFS was not reached (NR) for zanu and was 42.2 mo for BR (Figure). At 42 mo, estimated PFS rates were 82% for zanu. With additional follow-up, PFS for zanu versus BR was improved for pts with mutated IGHV (HR 0.35; 95% CI: 0.19, 0.64); benefit was also sustained for pts with unmutated IGHV (HR 0.23; 95% CI: 0.14, 0.37) or del(11q) (HR 0.26; 95% CI: 0.13, 0.51). Complete response/complete response with incomplete hematological recovery (CR/CRi) rates in pts w/o del(17p) were 17% and 22% with zanu and BR, respectively. While median OS was NR in either arm, HR for OS was 0.87 (95% CI: 0.50, 1.48) for zanu versus BR, and estimated 42-mo rates were 89% versus 88%, respectively. For pts with del(17p) assigned to zanu monotherapy, after a median follow-up of 47.9 mo, the estimated 42-mo PFS and OS rates were 79% and 90%, respectively; the CR/CRi rate was 15%. As of 31 Oct 2022, zanu treatment was ongoing in 75% pts w/o del(17p) and 70% pts with del(17p). The most common causes for treatment discontinuation were adverse events (AEs) and progressive disease for pts w/o del(17p) (15%, 6%) and with del(17p) (14%, 14%, respectively). AEs of interest (AEI) in pts w/o del(17p) (zanu vs. BR) included any-grade (gr) atrial fibrillation/flutter (5% vs. 3%), hypertension (18% vs. 14%), bleeding (49% vs. 12%), infection (73% vs. 63%), anemia (7% vs. 21%), thrombocytopenia (6% vs. 18%), and neutropenia (17% vs. 57%). Gr≥3 AEI included bleeding (6% vs. 2%), infection (24% vs. 22%), anemia (1% vs. 2%), thrombocytopenia (2% vs. 8%), and neutropenia (13% vs. 51%). Encore Abstract—previously submitted to EHA 2023 The research was funded by: BeiGene Keyword: chronic lymphocytic leukemia (CLL) Conflicts of interests pertinent to the abstract M. Shadman Consultant or advisory role: AbbVie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, BeiGene, Bristol Myers Squibb, Morphosys/Incyte, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune, Mustang Bio, Regeneron, Merck, Fate Therapeutics, MEI Pharma and Atara Biotherapeutics Research funding: Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, AbbVie, TG Therapeutics, BeiGene, AstraZeneca, Sunesis, Atara Biotherapeutics, Genmab, Morphosys/Incyte T. Munir Consultant or advisory role: Janssen, AbbVie, Lilly, AstraZeneca, BeiGene, Alexion, Sobi, Novartis Honoraria: Janssen, AbbVie, AstraZeneca, Roche, Sobi, Alexion Educational grants: Janssen, AbbVie, AstraZeneca T. Roback Honoraria: AstraZeneca, BeiGene, Janssen, AbbVie, Octapharma, Regeneron, GSK Research funding: BeiGene, OctaPharma, AstraZeneca, Janssen, Regeneron, GSK Educational grants: AstraZeneca J. R. Brown Consultant or advisory role: Abbvie, Acerta/Astra-Zeneca, BeiGene, Genentech/Roche, Grifols Worldwide Operations, Hutchmed, iOnctura, Janssen, Kite, Loxo/Lilly, MEI Pharma, Numab Therapeutics, Pfizer, Pharmacyclics Research funding: BeiGene, Gilead, iOnctura, Loxo/Lilly, MEI Pharma, TG Therapeutics B. S. Kahl Consultant or advisory role: Genentech, ADCT, AbbVie, AstraZeneca, BeiGene, Pharmacyclics, BMS, TG Therapeutics, Teva, Janssen, MEI Research funding: Genentech, ADCT, AbbVie, Acerta, AstraZeneca, BeiGene P. Ghia Consultant or advisory role: AbbVie, AstraZeneca, BeiGene, BMS; Janssen, Lilly/Loxo Oncology, MSD, Roche Honoraria: AbbVie, AstraZeneca, BeiGene, BMS; Janssen, Lilly/Loxo Oncology, MSD, Roche Research funding: AbbVie, AstraZeneca, BMS, Janssen K. Giannopoulos Employment or leadership position: Next Generation Hematology Consultant or advisory role: AbbVie, Amgen, AstraZeneca, BeiGene, GSK, Janssen, Novartis, Takeda, Roche, Gilead, Sandoz Honoraria: AbbVie, Amgen, AstraZeneca, BeiGene, Janssen, Novartis, Takeda, Roche, Karyopharm, GSK, Gilead, Sandoz, Pfizer, Teva Research funding: AbbVie, Amgen, AstraZeneca, Janssen, Sanofi-Genzyme, Novartis, Takeda, Roche Educational grants: Sanofi-Genzyme, Roche, Janssen M. Šimkovič Consultant or advisory role: AbbVie, AstraZeneca, Janssen-Cilag Stock ownership: AbbVie, AstraZeneca, J&J, BeiGene, Gilead, Baxter, Novartis, Abbot, Sanofi Honoraria: AbbVie, Janssen-Cilag, AstraZeneca Educational grants: AbbVie, Janssen-Cilag, AstraZeneca S. Opat Consultant or advisory role: AbbVie, BeiGene, AstraZeneca, BMS, CSL Behring, Gilead. Janssen, Merck, Roche, Takeda Honoraria: AbbVie, BeiGene, AstraZeneca, BMS, CSL Behring, Gilead. Janssen, Merck, Roche, Takeda Research funding: AbbVie, AstraZeneca, BeiGene, CSL Behring, Gilead. Janssen, Merck, Pharmacyclics, Roche, Takeda R. Greil Consultant or advisory role: Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Merck, Gilead, Daiichi Sankyo, Sanofi Honoraria: Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo, Sanofi Research funding: Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo Educational grants: Roche, Amgen, Janssen, AstraZeneca, Novartis, MSD, Celgene, Gilead, BMS, Abbvie, Daiichi Sankyo M. Trněný Employment or leadership position: First Faculty of Medicine, Charles University General Hospital in Prague Consultant or advisory role: Janssen, Gilead Sciences, Takeda, Bristol-Myers Squibb, Amgen, AbbVie, Roche, MorphoSys, Incyte, Novartis, Portolla Honoraria: Janssen, Gilead Sciences, Bristol-Myers Squibb, Amgen, AbbVie, Roche, AstraZeneca, MorphoSys, Incyte, Portolla, Takeda, Novartis Educational grants: Gilead, Takeda, Bristol-Myers Squibb, Roche, Janssen, AbbVie D. Brander Consultant or advisory role: AbbVie, Genentech, Pharmacyclics, Pfizer, TG Therapeutics, Verastem Research funding: AbbVie, ArQule, Ascentage, AstraZeneca, BeiGene, DTRM, Genetech, Juno/Celgene/BMS, LOXO, MEI Pharma, Novaris, Pharmacyclics, TG Therapeutics Other remuneration: NCCN panel member I. W. Flinn Consultant or advisory role: AbbVie, AstraZeneca, BeiGene, Century Therapeutics, Genentech, Genmab, Hutchison MediPharma, Iksuda Therapeutics, InnoCare Pharma, Janssen, Kite Pharma, MorphoSys, Myeloid Therapeutics, Novartis, Nurix Therapeutics, Pharmacyclics, Roche, Secura Bio, Servier Pharmaceuticals, Takeda, TG Therapeutics, Verastem, Vincerx Pharma, Xencor Research funding: AbbVie, Acerta Pharma, Agios, ArQule, AstraZeneca, BeiGene, Biopath, Bristol Myers Squibb, CALIBR, CALGB, Celgene, City of Hope National Medical Center, Constellation Pharmaceuticals, Curis, CTI Biopharma, Epizyme, Fate Therapeutics, Forma Therapeutics, Forty Seven, Genentech, Gilead Sciences, InnoCare Pharma, IGM Biosciences, Incyte, Infinity Pharmaceuticals, Janssen, Kite Pharma, Loxo, Merck, Millennium Pharmaceuticals, MorphoSys, Myeloid Therapeutics, Novartis, Nurix, Pfizer, Pharmacyclics, Portola Pharmaceuticals, Rhizen Pharmaceuticals, Roche, Seattle Genetics, Tessa Therapeutics, TCR2 Therapeutics, TG Therapeutics, Trillium Therapeutics, Triphase Research & Development Corp., Unum Therapeutics, Verastem, 2seventy bio E. Verner Research funding: Janssen Cilag A. Tedeschi Employment or leadership position: Department of Hematology Niguarda Hospital Milano Consultant or advisory role: Janssen spa, AstraZeneca, BeiGene, AbbVie Other remuneration: Speakers Bureau: Janssen spa S. De Guibert Honoraria: Janssen, AbbVie, Gilead, AstraZeneca K. Laribi Employment or leadership position: BeiGene, AbbVie, AstraZeneca, Novartis, Takeda Consultant or advisory role: BeiGene Honoraria: Seagen, BeiGene, AbbVie, Takeda Research funding: Novartis, BeiGene, AbbVie, Janssen T. Tian Employment or leadership position: BeiGene Stock ownership: BeiGene V. Ramakrishnan Employment or leadership position: BeiGene Stock ownership: BeiGene Y. Liu Employment or leadership position: BeiGene Ltd. Stock ownership: BeiGene Ltd. Educational grants: BeiGene Ltd. A. Szeto Employment or leadership position: BeiGene Stock ownership: BeiGene J. Paik Employment or leadership position: BeiGene Stock ownership: BeiGene A. Cohen Employment or leadership position: BeiGene Stock ownership: BeiGene Educational grants: BeiGene C. S. Tam Honoraria: Janssen, AbbVie, BeiGene, LOXO, AstraZeneca Research funding: Janssen, AbbVie, BeiGene W. Jurczak Research funding: AbbVie, AstraZeneca, BeiGene, Celgene, Debbiopharm, Epizyme, Incyte, Janssen, Merck, Roche, Takeda, TG Therapeutics

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