The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the approval of zanubrutinib for use in adult patients with marginal zone lymphoma who have received at least 1 prior anti–CD20-based therapy.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of zanubrutinib (Brukinsa) for use in adult patients with marginal zone lymphoma (MZL) who have received at least 1 prior anti–CD20-based therapy.1
The positive opinion is supported by findings from the phase 2 MAGNOLIA trial (NCT03846427), in which the BTK inhibitor elicited an overall response rate or 68.2% (95% CI, 55.56%-79.11%) in 66 patients with relapsed or refractory MZL who received at least 1 anti–CD20-based regimen. Among those who responded to zanubrutinib, 25.8% achieved a complete response (CR) and 42.4% experienced a partial response.2 The median time to response was 2.8 months (range, 1.7-11.1).
“There are currently no BTK inhibitors approved for MZL in Europe and with this positive opinion, we are one step closer to bringing forward a chemotherapy-free treatment option for this rare blood cancer,” Mehrdad Mobasher, MD, MPH, chief medical officer of Hematology at BeiGene, stated in a press release. “We look forward to a decision from the European Commission in the coming months.”
The single-arm, open-label MAGNOLIA trial enrolled patients who were at least 18 years of age, who had histologically confirmed MZL—including splenic MZL (SMZL), nodal MZL (NMZL), and extranodal MZL, mostly represented by mucosa-associated lymphoid tissue (MALT) disease—and who required systemic treatment. Patients were required to have an ECOG performance status of 0 to 2 and acceptable organ function.
Those who previously received a BTK inhibitor, had central nervous system involvement by MZL, known transformation to aggressive lymphoma, clinically relevant cardiovascular disease, and active infection, were excluded. Although those who required concurrent CYP3A inhibitors or inducers were excluded, those who received antiplatelet treatment and anticoagulants were allowed.
A total of 68 patients were enrolled to the trial, and they were given zanubrutinib at a twice-daily dose of 160 mg.
These patients had a median age of 70 years (range, 37-95), and 27.9% were aged 75 years or older. Most patients were Caucasian (60.3%), male (52.9%), and had an ECOG performance status of 0 (57.4%). Regarding MZL subtype, 38.2% of patients had NMZL, 38.2% had extranodal MZL, and 17.6% had SMZL. Four patients had concurrent nodal and extranodal disease and investigators were not able to classify the primary disease subtype.
All participants received at least 1 prior line of treatment with a CD20-directed agent. The median number of prior lines of systemic therapies received was 2 (range, 1-6). Notably, 32.4% of patients had refractory disease at the time of study entry. The most common prior therapies received were rituximab (Rituxan) plus cyclophosphamide, vincristine, and prednisolone (36.8%), rituximab plus bendamustine (32.4%), and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (25%).
The median treatment duration was 60.1 weeks (range, 3.7-85.1), and the median number of treatment cycles received was 15 (range, 1-21). A total of 66 patients were evaluable for efficacy.
Additional data published in Clinical Cancer Research showed that the ORRs for those with extranodal (n = 25), nodal (n = 25), splenic (n = 12), and unknown (n = 4) disease subtypes with zanubrutinib were 64%, 76%, 66.7%, and 50%, respectively. The independent review committee (IRC)–assessed CR rates for these subtypes were 40%, 20%, 8.3%, and 25%, respectively. Of the 17 total patients who achieved a CR with the BTK inhibitor, only 1 experienced progressive disease.
The IRC-assessed median duration of response (DOR) was not yet reached. The estimated DOR at 12 months following first response to zanubrutinib was 93.0% (95% CI, 79.8%-97.7%). Moreover, at a median follow-up of 15.7 months (range, 1.6-21.9), 89% of 45 responders were free from disease progression or death; 76% continued zanubrutinib.
The median progression-free survival (PFS) per IRC assessment was not reached. The estimated 12- and 15-month PFS rate was 82.5% (95% CI, 70.55%-89.93%). The median overall survival (OS) was also not reached. The estimated 12-month OS rate was 95.3% (95% CI, 86.0%-98.4%); the 15-month rate was 92.9% (95% CI, 81.9%-97.3%).
In terms of safety, zanubrutinib was found to have a favorable toxicity profile. The most common adverse reactions to occur in at least 30% of the pooled safety population (n = 847) included a reduction in neutrophil count, upper respiratory tract infection, decreased platelet count, and hemorrhage.
The cardiac effects observed with the agent proved to be consistent with what had been reported in prior studies of the BTK inhibitor, with low rates of atrial fibrillation (3%) and atrial flutter (0.4%).
Six percent of patients discontinued treatment because of toxicities.