Blood cancers

Urgent need for options after BTKi failure in mantle-cell lymphoma

There is an urgent need for new treatment options to improve survival in patients with relapsed/refractory mantle-cell lymphoma who have failed Bruton tyrosine kinase inhibitor (BTKi) therapy, say researchers who have reported the first large real-world dataset.

Analysis of data from a cohort of 240 patients across multiple European centres found an overall survival of 9.7 months once patients had moved on to other therapies because they relapsed or could not tolerate BTK inhibitor treatment.

The results from the SCHOLAR-2 study also showed the median overall survival from the start of first BTKi therapy was 14.6 in the overall cohort, 5.5 months in 91 patients without post-BTKi therapy, and 23.8 months in 149 patients who received post-BTKi therapy not including CAR-T treatment.

Among the patients who were treated between 2012 and 2018, 64% received BTKi therapy in the second line or third line of therapy, and 62% received subsequent treatments after BTKi discontinuation, the researchers reported in the British Journal of Haematology.

But although SCHOLAR-2 reflects recent clinical practice it does not include CAR T-cell therapies for which currently only brexucabtagene autoleucel is approved in Europe, the researchers said.

A smaller analysis of a subgroup of 59 patients who matched those enrolled in ZUMA-2 study suggested overall survival may have been better had CAR-T been available but it was unclear exactly who would have been eligible.

“There will still be a subset of patients who will not be able or eligible to receive CAR-T-cell therapy post-BTKi failure for various reasons. This highlights an important area for further research to improve access to CAR T-cell therapy and/or develop alternative effective treatments for those not eligible,” the researchers said.

They also noted that the study population included heavily pre-treated, high-risk patients with relapsed/refractory disease who had failed or could not tolerate BTK inhibitor therapy, which may not be representative of all mantle-cell lymphoma patients receiving BTK inhibitor treatment in clinical practice

Among those who received post-BTKi therapy with another agent, lenalidomide-containing regimens and bendamustine plus rituximab were most frequently administered.

The results “provide a benchmark for survival” in patients with relapsed/refractory mantle-cell lymphome receiving salvage therapy after BTKi failure, the researchers concluded.

Dr Toby Eyre, Haematology Consultant at Oxford University Hospitals NHS Foundation Trust told the limbic that the results show “outcomes are poor after covalent BTKi and that new therapeutic developments are still needed in relapsed mantle cell lymphoma”.

He also noted that many patients were not able to have another line of therapy, either because of choice, comorbidities, frailty or pace of their disease.

“Those patients have a particularly poor outcome, so there is a need to develop treatments that work in post-covalent BTKi that are accessible, tolerance and easy to deliver,” he said.

“This will become increasingly relevant as covalent BTK inhibitor therapy gradually moves to the front-line setting.” 

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