First results for zanubrutinib plus venetoclax in del(17p)/TP53-mutated CLL/SLL

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

Arm D of the phase 3 SEQUOIA trial (NCT03336333) exposed 66 participants with CLL/SLL and del(17p) and/or TP53 mutations to the combination regimen of Bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib plus the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. Prof. Paolo Ghia (University Vita-Salute San Raffaele, Italy) presented the preliminary results of this study [1].

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 measurable residual disease (<10^-4) rate was 59% in at least 1 peripheral blood sample (see Figure). The median progression-free survival was not reached at the time of presentation of the results, but the estimated 24-month progression-free survival rate was 94%.

Figure: Measurable residual disease rates in peripheral blood increased with longer treatment duration [1]



MRD, measurable residual disease; PB, peripheral blood.

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

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

1. Ma S, et al. Combination of Zanubrutinib plus venetoclax for treatment-naïve CLL/SLL with del(17p) and/or TP53: preliminary results from SEQUOIA arm D. S160, EHA congress 2024, 13–16 June, Madrid, Spain.

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Posted on 12 August 202412 August 2024