Dr. Flinn on the FDA Approval of Zanubrutinib in CLL/SLL

Ian Flinn, MD, PhD, director, Lymphoma Research, Sarah Cannon Research Institute at Tennessee Oncology; director, Sarah Cannon Transplant and Cellular Therapy Program, TriStar Centennial, discusses the significance of the FDA approval of zanubrutinib (Brukinsa) in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

On January 19, 2023, the FDA granted approval to zanubrutinib in patients with CLL or SLL. The regulatory decision was based on findings from the phase 3 SEQUOIA (NCT03336333) and ALPINE (NCT03734016) trials. SEQUOIA investigated zanubrutinib, a second-generation BTK inhibitor, vs bendamustine plus rituximab (Rituxan) in patients with previously untreated CLL or SLL. ALPINE evaluated the agent vs the BTK inhibitor ibrutinib (Imbruvica) in patients with relapsed/refractory CLL or SLL.

Dr. Flinn on the Benefits of Zanubrutinib in CLL/SLL

The FDA approval of zanubrutinib in CLL and SLL provides an additional treatment option for patients in both the frontline and relapsed settings, Flinn says. Zanubrutinib joins several treatment options that are already available for patients with CLL as another effective agent with a tolerable safety profile, Flinn explains.

Across both the ALPINE and SEQUOIA trials, adverse effects associated with zanubrutinib that occurred in at least 30% of patients were neutrophil count decrease, upper respiratory tract infection, platelet count decrease, hemorrhage, and musculoskeletal pain. Additionally, 3.7% of patients had atrial fibrillation or flutter, and 0.2% of patients had ventricular arrhythmias of grade 3 or higher.

Dr. Flinn on the Efficacy of Zanubrutinib in CLL/SLL

Although ALPINE and SEQUOIA were different studies in 2 different settings, zanubrutinib produced progression-free survival (PFS) and overall response rate (ORR) benefits in each, Flinn says. In SEQUOIA, the median PFS was not reached in patients who received zanubrutinib vs 33.7 months with chemoimmunotherapy. This PFS benefit was clinically meaningful and statistically significant, with a HR of 0.42, Flinn notes. Additionally, a separate, non-randomized cohort showed that zanubrutinib led to an ORR of 88% in patients with CLL or SLL with 17p deletion. These findings aligned with previous results of studies comparing BTK inhibitors with chemoimmunotherapy in the frontline CLL setting, Flinn explains.

More surprising results came from ALPINE, in which zanubrutinib demonstrated a median 24-month PFS rate of 78.4% and an ORR of 83.5%, vs 65.9% and 74.2%, respectively, with ibrutinib, Flinn says. In this trial, the agent also improved PFS in patients with 17p abnormalities, a historically difficult-to-treat population, Flinn concludes.

Editor’s Note: Dr Flinn has consulting roles with AbbVie, BeiGene, Century Therapeutics, Genentech, Genmab, Hutchison MediPharma, InnoCare Pharma, Kite Pharma, Myeloid Therapeutics, Novartis, Secura Bio, Servier Pharmaceuticals, TG Therapeutics, Vincerx Pharma, and Xencor and has received research grants from 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, Marker Therapeutics, Merck, Millennium Pharmaceuticals, MorphoSys, Myeloid Therapeutics, Novartis, Nurix, Pfizer, Pharmacyclics, Portola Pharmaceuticals, Rhizen Pharmaceuticals, Roche, Seattle Genetics, Step Pharma, Tessa Therapeutics, TG Therapeutics, Trillium Therapeutics, Triphase Research & Development Corp., Unum Therapeutics, Verastem, Vincerx Pharma, and 2seventy bio.