This protocol applies to patients with splenic marginal zone lymphoma (SMZL) and concurrent hepatitis C virus (HCV) infection whose disease has relapsed or become refractory after initial systemic therapy.
Hepatitis C virus infection is an important comorbidity in this population. SMZL patients with hepatitis C infection should receive up-front anti-viral therapy as part of initial management, which shapes the subsequent therapeutic landscape when relapse occurs.
The preceding line consisted of systemic therapy for symptomatic disease — including rituximab monotherapy, immunochemotherapy (bendamustine-rituximab, CVP, or CHOP), splenectomy, or radiotherapy. Escalation to this protocol is triggered when that treatment did not achieve a complete response: specifically, failure to resolve splenomegaly, failure to normalise cytopenias (haemoglobin, platelets, neutrophils), persistence of a clonal B-cell population in peripheral blood, or evidence of ongoing bone marrow infiltration.
For relapsed or refractory disease, the protocol considers rituximab-based regimens alongside targeted agents, including covalent BTK inhibitors — with additional options available for localised relapse. The complete eligibility criteria, preferred sequencing, and agent selection remain in the full protocol.
DOI: 10.1111/bjh.19064
SMZL patients with hepatitis C infection should receive up-front anti-viral therapy.
There is limited evidence that rituximab monotherapy can be effective for relapsed/refractory SMZL, including those who have progressed after rituximab monotherapy or splenectomy.
Bruton tyrosine kinase (BTK) plays a critical role in MZL pathogenesis, and several covalent BTK inhibitors (cBTKi) are approved for relapsed/refractory MZL.
Treatment for relapsed MZL follows a similar paradigm to relapsed/refractory follicular lymphoma, including RT for localised relapse and active surveillance for asymptomatic, advanced stage relapse.
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