Zanubrutinib in relapsed/refractory marginal zone lymphoma: MAGNOLIA

B-cell receptor-mediated signaling has been identified as a critical step in marginal zone lymphoma (MZL) pathogenesis [1]. Accordingly, BTK inhibition is effective in the management of patients with relapsed/refractory MZL, as shown for the first-generation BTK inhibitor ibrutinib [2]. The multicenter, single-arm, phase II MAGNOLIA study is evaluating the next-generation BTK inhibitor zanubrutinib 160 mg twice daily in patients with relapsed/refractory MZL including splenic, nodal and extra-nodal subtypes after pretreatment with ≥ 1 CD20-based regimen. The primary endpoint is the overall response rate (ORR) as determined by independent review based on the Lugano 2014 classification. At EHA 2021, Opat et al. reported the results of the study after completed enrollment [3]. A total of 68 patients had received ≥ 1 dose of zanubrutinib. The efficacy population included 66 individuals.

MAGNOLIA met its primary endpoint. After a median follow-up of 15.7 months, the ORR was 68.2 %, thus exceeding the prespecified null ORR of 30 % (p < 0.0001). Complete remissions emerged in 25.8 %. Responses were observed in all MZL subtypes and across patient and disease characteristics such as age, presence of bulky or extra-nodal disease, and type of pretreatment. Median progression-free survival and median duration of response had not been reached yet. At 15 months, 82.5 % of patients were alive and progression-free.

The most common treatment-emergent adverse events (TEAEs) of interest included infections (all grades, 45.6 %), hemorrhage (36.8 %), and diarrhea (22.1 %). Among grade ≥ 3 events, infections (16.2 %) and neutropenia (10.3 %) prevailed. Atrial fibrillation or flutter occurred in two patients (2.9 %). No major hemorrhage was reported. TEAEs led to dose interruptions in 29.4 %, while dose reductions were not necessary in any of the patients. In four cases, treatment was discontinued due to TEAEs unrelated to zanubrutinib. Overall, zanu­brutinib proved highly active and showed a favorable safety profile in patients with relapsed/refractory MZL.

REFERENCES

  1. Seiler T, Dreyling M, Bruton’s tyrosine kinase inhibitors in B-cell lymphoma: current experience and future perspectives. Expert Opin Investig Drugs 2017; 26(8): 909-915
  2. Noy A et al., Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood 2017; 129(16): 2224-2232
  3. Opat S et al., Phase 2 study of zanubrutinib in patients with relapsed/refractory marginal zone lymphoma (MAGNOLIA study). EHA 2021, EP783

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