Zanubrutinib Plus Venetoclax Shows Promise in Del(17p)/TP53-Mutated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Jul 13, 2024

Photo Credit: Nemes Laszlo

Zanubrutinib plus venetoclax delivered promising preliminary efficacy results in newly diagnosed CLL/SLL in participants with del(17p) and/or TP53 mutations.

The combination of zanubrutinib and venetoclax was associated with deep and durable responses in participants with previously untreated high-risk chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) and del(17p) and/or TP53 mutations, first results of the SEQUOIA trial showed.

Arm D of the SEQUOIA trial (NCT03336333) exposed 66 participants with CLL/SLL and del(17p) and/or TP53 mutations to the combination regimen of the Bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib plus the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. Prof. Paolo Ghia, MD, from the University Vita-Salute San Raffaele, in Italy, presented the preliminary results of this study¹.

After a median follow-up of 31.6 months, the overall response rate was 100% and the complete remission (CR) plus CR with incomplete count recovery rate was 48%. Importantly, the best undetectable minimal residual disease (<10^-4) rate was 59% in at least one peripheral blood sample. Finally, the median progression-free survival was not reached at this point. The estimated 24-month progression-free survival rate was 94%.

COVID-19 (55%), diarrhea (39%), nausea (30%), contusion (29%), and fatigue (23%) were the most frequently observed side effects with the combination regimen. “The safety profile was overall favorable and we did not see any unexpected issues,” commented Prof. Ghia.

In conclusion, zanubrutinib plus venetoclax delivered promising preliminary efficacy results in newly diagnosed CLL/SLL in participants with del(17p) and/or TP53 mutations.

Medical writing support was provided by Robert van den Heuvel.