Dismantling relapsed/refractory mantle cell lymphoma

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.