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Dismantling relapsed/refractory mantle cell lymphoma.

Christine E Ryan1, Anita Kumar2

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Summary

Effective treatment for relapsed or refractory mantle cell lymphoma (MCL) is challenging. Current Bruton tyrosine kinase (BTK) inhibitors are not curative, necessitating exploration of novel agents and combination therapies for improved outcomes.

Keywords:
Mantle cell lymphomaNovel agentsRelapsed/refractory diseaseTargeted therapies

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Area of Science:

  • Hematology
  • Oncology
  • Clinical Therapeutics

Background:

  • Mantle cell lymphoma (MCL) remains difficult to treat effectively in its relapsed or refractory (R/R) state, despite advances in non-Hodgkin lymphoma therapies.
  • Bruton tyrosine kinase (BTK) inhibitors have become a cornerstone for R/R MCL, yet they are not curative and present evolving treatment challenges.
  • The increasing use of BTK inhibitors in frontline settings necessitates a review of alternative and emerging strategies for R/R MCL.

Purpose of the Study:

  • To review current and emerging treatment strategies for relapsed or refractory mantle cell lymphoma (R/R MCL).
  • To evaluate the efficacy of established therapies including BTK inhibitors, venetoclax, lenalidomide, and CAR T-cell therapy.
  • To highlight novel agents and targeted therapies offering potential for improved outcomes in R/R MCL.

Main Methods:

  • Review of clinical trial data and published literature on treatment strategies for R/R MCL.
  • Analysis of data for BTK inhibitors, BCL2-inhibitor venetoclax, lenalidomide-based regimens, and chimeric antigen receptor T-cell therapy.
  • Evaluation of emerging agents such as antibody-drug conjugates, bispecific antibodies, and other targeted therapies.

Main Results:

  • BTK inhibitors are a mainstay but not curative for R/R MCL, leading to challenges in the evolving treatment landscape.
  • Established therapies like venetoclax, lenalidomide, and CAR T-cell therapy offer options for R/R MCL management.
  • Novel agents including antibody-drug conjugates and bispecific antibodies show promise for improved patient outcomes.

Conclusions:

  • While BTK inhibitors are central to R/R MCL treatment, their non-curative nature drives the need for alternative and novel therapeutic approaches.
  • A comprehensive understanding of current and emerging treatments, including targeted agents, is crucial for optimizing R/R MCL management.
  • Continued research into novel agents and combination strategies holds significant promise for improving long-term outcomes in R/R MCL patients.