Treatment of Relapsed or Refractory Mantle Cell Lymphoma

Patients with mantle cell lymphoma who have relapsed or become refractory to prior treatment represent a clinically challenging situation. The appropriate therapeutic strategy depends on what prior therapy was received — in particular, whether a covalent BTK inhibitor (cBTKi) was part of earlier treatment.

Clinical Scenario

Relapsed or refractory mantle cell lymphoma. This protocol addresses patients who have progressed on or become refractory to prior therapy, including those who received cBTKi-containing regimens as part of earlier treatment lines.

Treatment Approach

Following cBTKi-containing therapy, recognised treatment categories include cellular immunotherapy and next-generation targeted agents, among other options — each with specific eligibility considerations.

The complete evidence-based algorithm, including the full list of options, decision criteria, and regulatory approvals, is available in the structured protocol below.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1002/hem3.70233

For BTKi‑naïve patients with relapsed MCL, a cBTKi ± venetoclax (the latter not EMA‑ or FDA‑approved) should be offered as standard post‑first‑line immunochemotherapy.
Treatment options post‑cBTKi‑containing first‑line therapy include anti‑CD19 CAR‑T therapy (for patients at high risk of cBTKi failure) [III, A; FDA‑approved; EMA approval is after ≥ 2 prior lines of therapy].
Pirtobrutinib [III, A; EMA‑approved; FDA approval is after ≥ 2 prior lines of therapy].
Immunochemotherapy [IV, B].
cBTKi rechallenge ± venetoclax (the latter not EMA‑ or FDA‑approved) if prior intolerance or prior fixed duration only of cBTKi therapy [V, C].

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