Novel BTK inhibitor as good as established therapies for refractory marginal zone lymphoma

The next-generation selective Bruton tyrosine kinase inhibitor zanubrutinib appears to be safe and effective in the treatment of patients with relapsed/refractory marginal zone lymphoma (R/R MZL), as evidenced by high rates of objective response (ORR) and complete response (CR), according to data from the phase II MAGNOLIA (BGB-3111–214) study.

The single-arm, open-label study included 68 patients (median age 70 years, 52.9 percent male). Of these, 57.4 percent and 35.3 percent had ECOG performance status of 0 or 1, respectively. Twenty-six patients had nodal MZL (38.2 percent), another 26 had extranodal MZL (38.2 percent), and 12 had splenic MZL (17.6 percent); four (5.9 percent) patients presented with concurrent nodal and extranodal disease.

All 68 patients were treated with zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity. The median number of lines of prior systemic anticancer therapies was two.

Over a median follow-up of 15.7 months, the rates of ORR and CR were 68.2 percent and 25.8 percent, respectively, as assessed by an independent review committee (IRC). The corresponding ORR and CR rates by investigator assessment were 74.2 percent and 25.8 percent.

The median duration of response (DOR) and median progression-free survival (PFS) by IRC review was not reached. DOR rate at 12 months was 93.0 percent, and PFS rate was 82.5 percent at both 12 and 15 months.

Treatment was well tolerated. The majority of adverse events (AEs) were grade 1 or 2, with the most common being diarrhoea (22.1 percent), contusion (20.6 percent), and constipation (14.7 percent). Two patients experienced atrial fibrillation/flutter, and another developed grade 3 hypertension. AEs led to treatment discontinuation in four patients, although none of which were considered treatment-related.