Follicular lymphoma indication granted for zanubrutinib in the EU

24th November 2023

Zanubrutinib (brand name Brukinsa) has been granted marketing authorisation by the European Commission (EC) for use in combination with obinutuzumab for eligible patients with follicular lymphoma, its manufacturer BeiGene has announced.

This highly selective, oral Bruton’s tyrosine kinase (BTK) inhibitor is now approved for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma who have received at least two prior lines of systemic therapy.

The EC approval is based on positive results from the phase 2 ROSEWOOD study which looked at zanubrutinib plus obinutuzumab compared with the anti-CD20 monoclonal antibody obinutuzumab alone.

Some 217 patients with R/R follicular lymphoma who had received at least two prior lines of systemic therapy were included in the global, randomised, open-label study.

The primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival, and safety.

The researchers found the ORR to be 69.0% in the zanubrutinib plus obinutuzumab arm versus 45.8% in the obinutuzumab arm (P = 0.0012), with a median follow-up of approximately 20 months.

Responses were durable with 18-month landmark DOR of 69.3% in the zanubrutinib combination arm. Additionally, the median PFS for patients treated in the combination arm was 28.0 months, compared to 10.4 months for patients treated with only obinutuzumab (HR: 0.50 [95% CI: 0.33, 0.75]; P = 0.0007).

Zanubrutinib plus obinutuzumab was generally well-tolerated, with safety results consistent with previous studies of both medicines.

Zanubrutinib a ‘practice-changing option’

Dr Pier Luigi Zinzani, full professor of haematology at the Institute of Haematology ‘Seràgnoli’, University of Bologna, Italy, said: ‘People living with follicular lymphoma often experience relapse and have poor responses to subsequent lines of therapy, making it imperative to improve outcomes.

‘The results from the ROSEWOOD trial demonstrated a significant clinical benefit of Brukinsa plus obinutuzumab for patients with relapsed or refractory follicular lymphoma. Brukinsa is a chemotherapy-free, oral treatment option that can be a practice-changing option for eligible patients with relapsed or refractory follicular lymphoma.’

This is the fourth approved indication for this drug in the EU, which gives it ‘the broadest label of any medicine in its class globally’, according to Mehrdad Mobasher, chief medical officer, hematology at BeiGene.

In addition to R/R follicular lymphoma, zanubrutinib is approved in the EU as monotherapy for the treatment of adult patients with: chronic lymphocytic leukaemia, marginal zone lymphoma who have received at least one prior anti-CD20-based therapy, and Waldenström’s macroglobulinemia who have received at least one prior therapy, or in firstline treatment for patients unsuitable for chemo-immunotherapy.

The use of zanubrutinib in R/R follicular lymphoma is currently under review by regulatory authorities in Switzerland and the United Kingdom as part of the Access Consortium New Active Substance Work-sharing Initiative.

Zanubrutinib improves progression-free survival in relapsed lymphocytic leukaemia

21st December 2022

Zanubrutinib was superior to ibrutinib in patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma

In a head-to-head trial, zanubrutinib provided superior progression-free survival compared to ibrutinib in patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma, according the the results to a study by team of international researchers.

Chronic lymphocytic leukaemia (CLL) is an adult leukaemia characterised by abnormal accumulation of immunologically incompetent lymphocytes in blood, bone marrow, lymph nodes, and spleen and accounts for 25–30% of all leukaemias in Western Countries, leading to over 100,000 incident cases with more than 40,000 global deaths reported in 2019. In contrast, small lymphocytic lymphoma (SLL) comprises approximately 7% of newly-diagnosed cases of non-Hodgkin’s lymphomas although often at the time of diagnosis, most patients present with advanced-stage disease including generalised lymphadenopathy, hepatosplenomegaly and bone marrow involvement.

Bruton’s tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signalling and which is critical for proliferation and survival of leukaemia cells in many B cell malignancies. Moreover, oral irreversible BTK inhibitors such as ibrutinib, have been shown to provide a high response rates in patients with relapsed/refractory CLL and mantle-cell lymphoma. Zanubrutinib is a highly selective Bruton tyrosine kinase inhibitor that is well tolerated and demonstrated activity in patients with relapsed/refractory mantle cell lymphoma. In a multinational, phase 3, randomised trial, the same international research group, performed a head-to-head comparison of zanubrutinib with ibrutinib as treatment for relapsed or refractory CLL or small lymphocytic lymphoma (SLL). At a pre-specified interim analysis, the results showed that zanubrutinib provided a significantly higher overall response rate, lower atrial fibrillation rate and improved progression-free survival compared to ibrutinib after 15 months. In the current study, researchers provided an update on progression-free survival after nearly 30 months. In the trial, participants with relapsed or refractory CLL or SLL and who had received at least one previous course of therapy, were randomised 1:1 receive zanubrutinib at a dose of 160 mg twice daily or ibrutinib at a dose of 420 mg daily until the occurrence of disease progression or unacceptable toxic effects.

Zanubrutinib and progression-free survival

A total of 652 patients with a median age of 67 years (68.3% male) were included and randomised to zanubrutinib (327) or ibrutinib and followed for a median of 29.6 months.

In terms of progression-free survival, zanubrutinib was superior for disease progression or death with 87 vs. 118 occurrences of disease progression or death (hazard ratio, HR = 0.65, 95% CI 0.49 – 0.86, p = 0.002). At 24 months, the investigator-assessed rates of progression-free survival were 78.4% in the zanubrutinib group and 65.9% in the ibrutinib group.

Furthermore, the safety profile of zanubrutinib was better than ibrutinib, with fewer adverse events leading to treatment discontinuation and fewer cardiac events, including fewer cardiac events leading to treatment discontinuation or death.

The authors concluded that among those with relapsed or refractory CLL or SLL, progression-free survival was significantly longer among patients who received zanubrutinib and that the drug was associated with fewer cardiac adverse events.

Citation
Brown JR et al. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med 2022