Chemoimmunotherapy (CIT), immunotherapy and chemotherapy regimens are commonly used for the treatment of patients with marginal zone lymphoma. Moreover, the BTK inhibitor zanubrutinib has shown activity in the relapsed/refractory setting based on the phase II, single-arm MAGNOLIA and BGB-3111-AU-003 trials [1, 2]. Walewska et al. conducted a matching-adjusted indirect comparison (MAIC) to estimate the comparative efficacy of these treatment strategies in relapsed/refractory marginal zone lymphoma [3]. Individual patient-level data from 86 efficacy-evaluable patients enrolled in MAGNOLIA and BGB-3111-AU-003 were used to inform the zanubrutinib treatment group, resulting in an effective sample size of 38 individuals. Regarding CIT, immunotherapy and chemotherapy, aggregate data from a comparable cohort of 90 patients were identified from a UK cancer registry called the Haematological Malignancy Research Network. In both groups, a quarter of patients was refractory to the last therapy, and half had experienced progression within 24 months of initiation of treatment.

Relative to CIT, immunotherapy, or chemotherapy, zanubrutinib significantly reduced the risk of progression (adjusted HR, 0.30; p = 0.0014; Figure). The same applied to the endpoint of overall survival (adjusted HR, 0.23; p = 0.0002). Model results excluding patients who only received chemotherapy were consistent with these findings. The leave-one-out analyses showed that removing any one of the characteristics did not significantly alter the treatment effect estimates, although the number of prior lines of therapy had the largest impact. Taken together, these MAIC results suggest that zanubrutinib can be considered an effective alternative to CIT, immunotherapy, or chemotherapy, adding to a body of evidence that informs the relative efficacy of treatment options in patients with relapsed/refractory marginal zone lymphoma.

REFERENCES

1. Opat S et al., The MAGNOLIA trial: Zanubrutinib, a next-generation Bruton tyrosine kinase inhibitor, demonstrates safety and efficacy in relapsed/refractory marginal zone lymphoma. Clin Cancer Res 2021; 27(23): 6323-6332
2. Phillips T et al., Zanubrutinib monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Adv 2022; 6(11): 3472-3479
3. Walewska R et al., Matching-adjusted indirect comparison of zanubrutinib versus real-world chemoimmunotherapy or chemotherapy in relapsed/refractory marginal zone lymphoma. EHA 2024, abstract P1123

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