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Posted by on Dec 31, 2022 in Leukemia | 0 comments

In a nutshell

This study investigated the effectiveness and safety of zanubrutinib (Brukinsa) versus bendamustine (Treanda) plus rituximab (Rituxan) in untreated patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The data showed that zanubrutinib significantly improved the survival without cancer worsening versus bendamustine plus rituximab with manageable side effects in these patients.

Some background

CLL is a type of cancer that affects the immune system. SLL is a type of non-Hodgkin lymphoma (NHL). CLL and SLL are considered different manifestations of the same medical condition. An older standard treatment for CLL/SLL involves combining the chemotherapy drug bendamustine and immunotherapy drug rituximab. Targeted therapies like tyrosine kinase inhibitors (TKIs) are also used for the treatment of leukemia/lymphoma.

Bruton tyrosine kinase (BTK) inhibitors are a type of targeted therapy. They have shown effectiveness in the treatment of cancers such as CLL or SLL. Zanubrutinb is a newer generation BTK inhibitor effective in the treatment of CLL. It is more selective and has fewer off-target effects. However, the effectiveness and safety of zanubrutinib compared to bendamustine plus rituximab (BRin untreated patients with CLL and SLL are still unknown.

Methods & findings

This study involved 590 patients with CLL and SLL. The 17p chromosome deletion has an impact on CLL prognosis and is a high-risk marker. Patients without 17p chromosome deletion were randomly assigned into two groups. Group 1 included 241 patients who received zanubrutinib. Group 2 included 238 patients who received BR treatment. Group 3 included 111 patients with 17p chromosome deletion who received zanubrutinib. The average follow-up time was 26.2 months.

The average survival without cancer worsening was not reached (exceeded the average follow-up time) in both group 1 and group 2. Patients in group 1 were 58% more likely to survive without cancer worsening than patients in group 2.

Serious side effects occurred in 37% of the patients in group 1, 50% of the patients in group 2, and 41% of the patients in group 3. The most common side effect was low white blood cell counts.

The bottom line

This study concluded that zanubrutinib significantly improved survival without cancer worsening compared to bendamustine plus rituximab with manageable side effects in untreated patients with CLL and SLL.

The fine print

This study was funded by BeiGene, the manufacturer of zanubrutinib. This study had a short follow-up period. Longer-term studies are needed to fully evaluate the safety and effectiveness of zanubrutinib compared to the BR regimen in these patients. 

Published By :

The Lancet. Oncology

Date :

Jul 07, 2022

Original Title :

Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial.

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