Splenic marginal zone lymphoma
ICD-10 C88.4 · ICD-11 2A82.Y

SMZL Without Hepatitis C: Treatment When First-Line Therapy Has Failed

This protocol applies to patients with splenic marginal zone lymphoma (SMZL) who do not have hepatitis C infection, who had a clinical indication for treatment, and whose disease relapsed or did not achieve an adequate response after first-line systemic therapy.

Patient Scenario

The patient has SMZL without hepatitis C infection. An indication for treatment was present — including B symptoms, progressive cytopenia, symptomatic splenomegaly, bulky lymphadenopathy, autoimmune phenomena, or disease compromising vital organs. First-line therapy was initiated accordingly.

First-Line Treatment — Failure Condition

Initial management — which may have included rituximab monotherapy, immunochemotherapy combinations, or splenectomy — did not achieve a complete response. Complete response required:

Failure to reach these endpoints defines relapsed or refractory SMZL and escalates management to this next-line protocol.

Next-Line Approach (Partial Overview)

Several categories of agents are available for relapsed or refractory SMZL — including targeted therapies acting on key B-cell signalling pathways and immunotherapy-based combinations. The full options, selection criteria, and sequencing are detailed in the structured protocol.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1111/bjh.19064

The main criteria for treatment include constitutional symptoms, symptomatic or progressive splenomegaly, bulky lymphadenopathy, autoimmune phenomena and progressive cytopenias, as shown in Table 9.

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.

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.

Bruton tyrosine kinase (BTK) plays a critical role in MZL pathogenesis, and several covalent BTK inhibitors (cBTKi) are approved for relapsed/refractory MZL.

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