Mantle cell lymphoma real-world treatment patterns and outcomes, with a focus on BTK inhibitors

Evaluation of US real-world treatment patterns and outcomes for mantle cell lymphoma supports the use of BTK inhibitors as frontline treatment in frail patients and potentially to improve outcomes with del17p/TP53 mutations.

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Analysis of a decade of real-world data (RWD) on mantle cell lymphoma (MCL) treatment and outcomes in the USA has been published in Blood Advances. It shows that chemoimmunotherapy with bendamustine plus rituximab (BR) was the preferred frontline regimen and Bruton tyrosine kinase (BTK) inhibitors were the most common targeted agents used, primarily in second or later lines of therapy following relapse. Results show that MCL patients treated with first-line BTK inhibitors have a median survival of about 35 months and suggest that BTK inhibitor treatment may negate the impact of del17p/TP53 mutations.

MCL is a subtype of non-Hodgkin’s lymphoma, accounting for 5­­–10% of cases. It is currently considered incurable with available chemoimmunotherapy approaches and requires multiple successive lines of treatment to treat relapse and as chronic suppressive therapy. As our understanding of the pathophysiology of MCL has improved, as well as alternative induction chemotherapy regimens, newer targeted therapies have been developed, including BTK inhibition.

This study is the largest to date of RWD for MCL treatment and outcome patterns, and in regard to BTK therapy provides important evidence on utilization and outcomes of BTK inhibitors in routine clinical practice to complement prior learnings from clinical trials. All data were abstracted from electronic health records of 4049 MCL patients, median age 69 years, held by Flatiron Health, Inc. over the period of 2011–21.

The analysis showed bendamustine plus rituximab induction chemoimmunotherapy was the most used frontline regimen (42%).  Maintenance rituximab or consolidative autologous stem-cell transplant was noted in 31% of all patients. BTK inhibitors were the most preferred targeted agents in second or later lines of therapy (57%). Among patients treated with BTK inhibitors, the median real-world overall survival was 35 months (95% CI, 27-50), 24 months (95% CI, 22-30), and 18 months (95% CI, 14-21) for first, second, and third or later lines of therapy, respectively.

5% of patients in the study had a 17p deletion or TP53 mutation, and 7% of patients had blastoid variant MCL. These subsets were all associated with shorter overall survival. Interestingly, the presence of chromosome 17p deletion or TP53 mutation did not shorten the overall survival in BTK inhibitor treated patients. This mitigation of the negative influence of del17p/TP53-mutated MCL will be a focus for future investigation.

These findings led the study authors to conclude: “our study provides preliminary evidence supporting the use of BTK inhibitors in frail patients who are unable to tolerate intensive frontline chemoimmunotherapy.” Multiple clinical trials incorporating BTK inhibitors into frontline MCL therapy are ongoing and frontline BTK inhibitor use has already begun to percolate into routine clinical practice for the elderly and unfit patients. The real-world evidence generated in the study presented here will further encourage these developments.