Blood cancers

Zanubrutinib highly active and tolerable in marginal zone lymphoma

The selective bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib has shown promise as a novel, more effective and tolerable therapy for patients with relapsed/refractory marginal zone lymphoma (MZL).

The phase 2, single arm, open label MAGNOLIA study, presented at Blood 2021, comprised 68 patients with R/R MZL treated with 160mg zanubrutinib twice daily until disease progression or unacceptable toxicity.

The patients, recruited from nine countries including Australia, had nodal (38.2%), extranodal (38.2%), splenic (17.6%) and unknown (5.9%) MZL subtypes.

The study, concurrently published in Clinical Cancer Research, said the median number of lines of prior systemic anticancer therapies was two including rituximab.

The investigators found the IRC-assessed ORR was 68.2% overall – 64% for the extranodal, 76% for nodal, 66.7% for splenic, and 50% for unknown MZL subtypes.

The median time to response was 2.8 months.

Overall, 42.4% of patients achieved a partial response while 25.8% of patients achieved a complete response.

“Among the 17 patients who achieved CR, only one patient had disease progression and 13 patients remain on study treatment,” the study said.

“At a median study follow-up of 15.7 months, 40 (89%) of the 45 responders were free from progression or death with 34 (76%) patients continuing on zanubrutinib.”

The study reported that seven patients died including four due to disease progression and three due to adverse events.

“The 12- and 15-month OS rates were 95.3% and 92.9%, respectively.”

Adverse events of any grade were reported by almost all patients (95.6%) and 39.7% had at least one grade ≥3 event including neutropenia (10.3%), thrombocytopenia (4.4%), and COVID-19 pneumonia (4.4%).

Dose interruptions due to adverse events occurred in 29.4% of patients and four patients permanently discontinued zanubrutinib, although the events were assessed as unrelated to the study treatment.

Professor Stephen Opat, from Monash Health, told Blood 2021, that zanubrutinib was designed to maximise BTK occupancy and minimise off-target inhibition of TEC- and EGFR-family kinases.

All grade treatment-emergent adverse events of interest included infection (45.6%), haemorrhage (36.8%) but no major haemorrhage, diarrhoea (22.1%), thrombocytopenia (14.7%) and neutropenia (13.2%).

Only 2 patients (2.9%) had atrial fibrillation.

He concluded that the MAGNOLIA study met its primary endpoint and was highly active with a favourable safety profile.

The study was funded by BeiGene.

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