Mantle Cell Lymphoma (Age ≤65, Fit): What to Do When First-Line Therapy Does Not Achieve Undetectable MRD

This protocol addresses primary ovarian lymphoma in the specific context of mantle cell lymphoma in fit patients aged 65 years or younger, where first-line treatment has not resulted in undetectable minimal residual disease — the outcome that would otherwise indicate adequate disease control.

Clinical Scenario

Patient has mantle cell lymphoma, is fit, and is aged 65 years or under. In this population, first-line therapy is selected with undetectable minimal residual disease (MRD) following induction as the primary therapeutic benchmark.

First-Line Failure — Escalation Trigger

First-line therapy — comprising either a covalent BTK inhibitor-containing regimen or rituximab with high-dose cytarabine-based induction — did not achieve undetectable minimal residual disease following induction. This failure to reach the MRD endpoint is the condition that triggers escalation to the present protocol.

Approach in This Relapsed / Refractory Setting

The protocol defines a set of options involving covalent BTK inhibitor-based therapy as well as other approaches, with selection depending on prior treatment history and individual patient factors. The full eligibility criteria, sequencing, and decision algorithm are available in the structured protocol.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1016/j.annonc.2025.07.014

Fit patients ≤65 years (up to 70 years at physician's discretion) should receive one of the following first-line options, with a covalent BTKi (cBTKi) within the regimen preferred:

A cBTKi with or without venetoclax (cBTKi—venetoclax is not EMA or FDA approved) can be offered as standard after first-line immunoChT for the following:

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