Ever wondered what difference achieving better than uMRD4 means to your likely overall survival? German CLL SG are finding out - CLL11 trial

[AussieNeil]

From Detecting measurable residual disease beyond 10-4 through an IGHV leader-based NGS approach improves prognostic stratification in CLL

doi.org/10.1182/blood.20220...

Key Points from the German CLL Study Group

An academically-developed IGHV leader-based NGS assay can routinely detect and quantify MRD to 10-5 and beyond in CLL

MRD quantification below 10-4 using this assay improves prognostic stratification in CLL

The sensitivity of conventional techniques for reliable quantification of minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) is limited to MRD 10-4. Measuring MRD <10-4 could help to further distinguish between CLL patients with durable remission and those at risk of early relapse. We here present an academically developed IGHV leader-based next-generation sequencing (NGS) assay for the quantification of MRD in CLL. We demonstrate, based on measurements in contrived MRD samples, that the linear range of detection and quantification of our assay reaches beyond MRD 10-5. If provided with sufficient DNA input, MRD can be detected down to MRD 10-6.

This work is important for two reasons:-

1) International cooperation on standardising uMRD testing

2) Per the attached plots Measuring MRD <10-4 could help to further distinguish between CLL patients with durable remission and those at risk of early relapse.So therapy can be refined, for example extending the treatment time, or switching from time limited to maintenance therapy.

This is an open (unlocked) post

Neil

[bennevisplace]

Thanks Neil. This is evidently important work.

Does this "IGHV leader-based NGS assay" differ from standard NGS?

Are results like these the writing on the wall for flow cytometry in MRD assessment?

[AussieNeil Partner Administrator in reply to bennevisplace]

These are probably questions better answered by @gardening-girl.

Neil

[Indolent]

The evidence continues to mount that MRD negative might be a useful indicator for when to stop treatment. Understandably, most doctors are not ready to make that call, but it certainly does seem likely to occur. The only hangup might be the willingness of insurance companies to pay for the tests. But given the high cost of CLL drugs, they would probably see a cost benefit if they could shorten treatment times without reducing patient survival.

[BobbyFour]

More steps to get CLL into truly being a chronic disease!