Mantle Cell Lymphoma

At the 18th ICML in Lugano, Prof Dr Virginie De Wilde from the Institut Jules Bordet, HUBruxelles, highlighted notable presentations on the management of mantle cell lymphoma. A wide range of information was presented, covering four key areas: biomarkers, MRD results, first-line treatment options for both young and elderly patients, and some second-line treatment approaches. 

More accurate classification of mantle cell lymphoma (MCL) patients is necessary, surpassing conventional prognostic scores. Including biomarkers such as p53 mutations, 17q deletions, and other markers like CCND1 is now regarded as crucial. These biomarkers are accessible through standard methods, such as NGS and karyotyping, and their integration can inform treatment decisions. 

A substantial amount of information was presented on minimal residual disease (MRD) response, emphasising how MRD is assessed in both blood and bone marrow using eight-colour flow cytometry. This technique is available in most laboratories conducting immunophenotyping and is anticipated to become standard practice soon. Although the exact methods for tailoring treatment based on MRD results are not yet fully understood, this area is under close examination. For example, the TRIANGLE trial demonstrated that adding ibrutinib to standard treatment with rituximab and/or transplantation enhanced MRD negativity. MRD negativity has been linked to improved PFS and OS. Nonetheless, MRD remains a dynamic process, and its assessment at various stages of treatment and maintenance requires further investigation.

The TRIANGLE study has provided crucial insights into first-line treatment for young patients with MCL. It compares standard treatment with chemotherapy, transplantation, and maintenance, alongside two arms where ibrutinib is added—one with and one without transplantation. The addition of ibrutinib has been shown to improve both PFS and OS, making it a vital component in treatment. The key question now is not whether to include ibrutinib, but rather which patients should receive transplantation. While most may not benefit from it, careful monitoring is essential, particularly for patients with poor prognostic factors such as blastoid features or P53 mutations, as they may still benefit from transplantation. 

For elderly patients with MCL, the introduction of BTK inhibitors in first-line treatment is becoming a standard approach. The disappointing results from the SHINE study, adding ibrutinib to bendamustine-rituximab, did not lead to approval for ibrutinib in this setting. However, the ECHO trial, which investigated bendamustine-rituximab with or without acalabrutinib, demonstrated improved PFS and response rates for the acalabrutinib arm, even in patients with poor prognostic factors such as P53 mutations or blastoid features. This highlights the potential of BTK inhibitors in first-line treatment for elderly patients. While chemotherapy may still be relevant for some high-risk patients, such as those with blastoid variants, the use of BTK inhibitors in both young and elderly patients is recommended. Ibrutinib is preferred for younger patients, while acalabrutinib is more suitable for elderly patients based on the findings from the Triangle and ECHO trials.

In the context of relapse, a broad spectrum of treatment options exists, including bispecific antibodies, CAR-T cells, and various targeted therapies, along with combination approaches like doublets, triplets, and CAR-T grouplets. In Belgium, patients may receive pirtobrutinib, a non-covalent BTK inhibitor, after progression on covalent BTK inhibitors, offering a notable benefit due to the absence of cross-resistance. CAR-T cell therapy is also available as a third-line option. Furthermore, ongoing trials such as the OAsis trial are investigating new molecules and combinations, showing promising results for relapsed cases. These developments expand the range of effective treatments for patients with relapsed MCL.