Health Canada has approved the BTK inhibitor zanubrutinib for use in the treatment of adult patients with mantle cell lymphoma who have previously received at least 1 therapy.
Health Canada has approved the BTK inhibitor zanubrutinib (Brukinsa) for use in the treatment of adult patients with mantle cell lymphoma (MCL) who have previously received at least 1 therapy, according to an announcement from BeiGene, Ltd.1
The regulatory decision is based on data from 2 single-arm clinical trials. Across the trials, zanubrutinib elicited an overall response rate (ORR) of 84% per independent review committee (IRC) and 2014 Lugano classification.
Data from the phase 2 BGB-3111-AU-206 trial (NCT03206970) showed that at a median follow-up of 18.5 months, the ORR achieved with the BTK inhibitor was 84% (95% CI, 74%-91%); this included a complete response (CR) rate of 69% and a partial response (PR) rate of 15%. The median duration of response (DOR) achieved with the agent was 19.5 months (95% CI, 16.6–not evaluable).
Findings from the phase 1/2 BGB-3111-AU-003 trial (NCT02343120) demonstrated that at a median follow-up of 18.8 months, zanubrutinib induced an ORR of 84% (95% CI, 67%-95%), which included a CR rate of 25% and a PR rate of 59%. The median DOR with zanubrutinib was 18.5 months (95% CI, 12.6–NE).
“For many patients treated with previously-approved BTK inhibitors for MCL, adequate responses are not achievable, or they can be forced to discontinue treatment early due to side effects,” John Kuruvilla, MD, FRCPC, associate professor of medicine at the University of Toronto and clinical investigator at the Princess Margaret Cancer Centre, stated in the press release. “Today, we have a new option for our adult patients in Canada who have received 1 prior systemic or targeted therapy and are living with MCL, an aggressive blood cancer that is often diagnosed at a more advanced stage.”
In the open-label, multicenter BGB-3111-206 trial, 86 adult patients with MCL who had previously received 1 to 4 prior treatment regimens were given zanubrutinib at a twice-daily dose of 160 mg.2 Treatment was given until progressive disease or intolerable toxicity. The primary end point of the study was ORR per IRC using PET-based imaging and according to Lugano classification.
The median age of participants on this trial was 60.5 years (range, 34-75), 78% were male, 52.3% of patients had refractory disease, and 47.7% had relapsed disease. Moreover, 90.7% of patients had stage III/IV disease. Fifty-eight percent of patients had low-risk disease per the Mantle Cell Lymphoma International Prognostic Index (MIPI), and 29% and 13% had intermediate- and high-risk disease, respectively.
Additionally, 8.1% of patients had bulky disease that was greater than 10 cm, 43% had disease that was greater than 5 cm, and 14% had blastoid variant of MCL. Seventy-one percent of patients had extranodal disease. The median number of prior therapies received was 2 and the most frequent prior regimens were CHOP-based (91%) and rituximab (Rituxan)-based (74%).
The international BGB-3111-AU-003 trial included 32 patients with MCL who had received previous treatment and were given zanubrutinib at a twice-daily dose of 160 mg or a once-daily dose of 320 mg.3 Here, the median age of patients was 70 years (range, 42-86), with 38% of patients older than 75 years. Moreover, 69% of patients were male and 78% were Caucasian. Regarding risk, the MIPI score was low in 28% of patients, intermediate in 41% of patients, and high in 31% of patients.
Of 118 patients who previously received at least 1 therapy and zanubrutinib on the trials, 13.6% discontinued treatment because of adverse effects (AEs). The toxicity was frequently reported with the BTK inhibitor was pneumonia, which was experienced by 3.4% of patients. Moreover, 3.4% of patients experienced toxicities that led to dose reductions; these effects included hepatitis B, neutropenia, allergic dermatitis, and peripheral sensory neuropathy (n = 1, each).
Pooled data on 779 patients with B-cell malignancies who received treatment with zanubrutinib on clinical trials indicated that the most frequent AEs experienced with the agent were neutropenia, thrombocytopenia, upper respiratory tract infection, anemia, rash, musculoskeletal pain, diarrhea, cough, contusion, pneumonia, urinary tract infection, hemorrhage, and hematuria.
Eighteen percent of patients had serious adverse reactions. The most common serious reactions were pneumonia and hemorrhage, which were reported in 10.0% and 2.1% of patients, respectively.
In November 2019, the FDA granted an accelerated approval to zanubrutinibfor the treatment of adult patients with MCL who have previously received at least 1 therapy.4 The decision was also based on data from the 2 single-arm trials.