Zanubrutinib Versus Bendamustine and Rituximab in Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Median 5-Year Follow-Up of SEQUOIA

Mazyar Shadman ¹, Talha Munir ², Tadeusz Robak ³

¹Fred Hutchinson Cancer Center, University of Washington, Seattle, WA.
²Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.
³Copernicus Memorial Hospital, Medical University of Łódź, Łódź, Poland.
⁴Dana-Farber Cancer Institute, Boston, MA.
⁵Siteman Cancer Center, Washington University School of Medicine, St Louis, MO.
⁶Università Vita-Salute San Raffaele, Milano, Italy.
⁷IRCCS Ospedale San Raffaele, Milano, Italy.
⁸Experimental Hematooncology Department, Medical University of Lublin, Lublin, Poland.
⁹Hematology Department, St John's Cancer Centre, Lublin, Poland.
¹⁰4th Department of Internal Medicine-Haematology, Faculty of Medicine in Hradec Králové, University Hospital and Charles University in Prague, Hradec Králové, Czech Republic.
¹¹Department of Hematology, Karolinska University Hospital Solna, Stockholm, Sweden.
¹²Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
¹³Peninsula Health and Peninsula Private Hospital, Frankston, Melbourne, VIC, Australia.
¹⁴Lymphoma Research Group, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
¹⁵Department of Hematology, Copernicus Regional Oncology Centre, Gdansk, Poland.
¹⁶Third Medical Department With Hematology, Medical Oncology, Rheumatology and Infectiology, Paracelsus Medical University, Salzburg, Austria.
¹⁷Salzburg Cancer Research Institute Center for Clinical Cancer and Immunology Trials, Salzburg, Austria.
¹⁸Cancer Cluster Salzburg, Salzburg, Austria.
¹⁹Department of Haematology, Waitemata District Health Board, Takapuna, New Zealand.
²⁰Hematology Unit, Santa Maria delle Croci Hospital, Ravenna, Italy.
²¹First Department of Medicine, First Faculty of Medicine, Charles University, General Hospital, Prague, Czech Republic.
²²Hematologic Malignancies and Cellular Therapy, Duke University School of Medicine, Durham, NC.
²³Tennessee Oncology/OneOncology, Nashville, TN.
²⁴Department of Hematology and Cancer Prevention, School of Public Health, Silesian Medical University, Katowice, Poland.
²⁵Concord Repatriation General Hospital, Concord, NSW, Australia.
²⁶University of Sydney, Sydney, NSW, Australia.
²⁷Department of Hematology, Azienda Socio Sanitaria Territoriali Grande Ospedale Metropolitano Niguarda, Milan, Italy.
²⁸Hôpital de Pontchaillou, Rennes, France.
²⁹Department of Chemotherapy of Hemoblastosis, Blokhin Russian Cancer Research Center, Moscow, Russia.
³⁰Hematology Department, Centre Hospitalier du Mans, Le Mans, France.
³¹Unidad de Citogenetica Molecular, Servicio de Hematología, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
³²The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
³³BeiGene USA, Inc, San Mateo, CA.
³⁴Alfred Health and Monash University, Melbourne, VIC, Australia.
³⁵Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Poland.

⁰Fred Hutchinson Cancer Center, University of Washington, Seattle, WA.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology +

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December 8, 2024

View abstract on PubMed

Summary

Long-term results from the SEQUOIA trial show zanubrutinib significantly improves progression-free survival in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma compared to chemoimmunotherapy.

Area Of Science

Oncology
Hematology
Clinical Trials

Background

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a common B-cell malignancy.
Treatment-naïve patients often receive chemoimmunotherapy, but novel targeted agents are emerging.
The SEQUOIA trial previously demonstrated improved progression-free survival (PFS) with zanubrutinib.

Purpose Of The Study

To report updated long-term outcomes from the phase III SEQUOIA trial.
To compare zanubrutinib with bendamustine plus rituximab (BR) in treatment-naïve CLL/SLL patients.
To assess overall survival (OS) and safety at extended follow-up.

Main Methods

Phase III, randomized, open-label trial (NCT03336333).
Compared oral Bruton tyrosine kinase inhibitor zanubrutinib to BR.
Median follow-up of 61.2 months.

Main Results

Median PFS not reached with zanubrutinib vs. 44.1 months with BR (HR, 0.29; P=.0001).
Zanubrutinib demonstrated prolonged PFS in both mutated and unmutated IGHV subgroups.
Median OS not reached in either arm; 60-month OS rates were similar (85.8% vs. 85.0%).

Conclusions

Updated long-term data confirm superior PFS with zanubrutinib in treatment-naïve CLL/SLL.
Zanubrutinib represents a favorable and effective treatment option for this patient population.
No new safety concerns identified; adverse events consistent with known profiles.

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