We would like to request that the Diffuse Large B-Cell Lymphoma guidelines include circulating tumor DNA minimal residual disease (ctDNA-MRD) assessment using the Foresight CLARITYTM test, based on PhasED-Seq technology.

Specifically, we request the addition of ctDNA-MRD assessment using Foresight’s MRD test as part of the “PR or Progressive Disease” pathway at the end of 1L therapy as an option to adjudicate a positive PET scan in addition to biopsy.

- BCEL-4, 5, 6 PR or Progressive Disease Pathway: repeat biopsy or ctDNA-MRD assessment, if available

- Footnote U: Repeat biopsy or ctDNA-MRD assessment should be strongly considered in PET-positive patients prior to additional therapy. If biopsy or ctDNA-MRD negative, follow PET-negative pathway. In cases where biopsy cannot be done or is unsafe, clinical judgement and/or ctDNA-MRD should be used, if available.

We would like to request that the Diffuse Large B-Cell Lymphoma guidelines include circulating tumor DNA minimal residual disease (ctDNA-MRD) assessment using the Foresight CLARITYTM MRD test, based on PhasED-Seq technology.

Specifically, we request the addition of ctDNA-MRD assessment using Foresight’s MRD test during end-of-treatment response and follow-up as part of the CR pathway.

- BCEL-4, 5 CR Pathway: Consider ctDNA-MRD assessment during END-OF-TREATMENT RESPONSE.

- BCEL-6 CR Pathway: In addition to Observation or ISRT, include consideration of ctDNA-MRD assessment during END-OF-TREATMENT RESPONSE

- BCEL-4, 5, 6 CR Pathway: In addition to Clinical and Imaging follow-up, include Molecular follow-up with ctDNA-MRD assessment during FOLLOW-UP.

- BCEL-4, 5,6: Include an additional footnote specifying that if ctDNA-MRD positive, consider clinical trial or additional short interval surveillance with ctDNA-MRD and/or PET-CT or CT scan. If ctDNA-MRD negative, follow CR pathway.

We would like to request that the Diffuse Large B-Cell Lymphoma guidelines include circulating tumor DNA minimal residual disease (ctDNA-MRD) assessment using the Foresight CLARITYTM MRD test, based on PhasED-Seq technology.

Specifically, we request the addition of ctDNA-MRD assessment using Foresight’s MRD test during follow-up for relapse or refractory disease.

- BCEL-9: In addition to Clinical and Imaging follow-up, add Molecular follow-up with ctDNA-MRD assessment during FOLLOW-UP.

In light of the requested inclusion of circulating tumor DNA minimal residual disease (ctDNA-MRD) assessment using the Foresight CLARITYTM MRD test in the Diffuse Large B-Cell Lymphoma guidelines, we also request inclusion of ctDNA-MRD assessment in the BCEL guidelines. We believe this would be appropriate in the listing of prognostic tools in BCEL-A or as a new page describing response definitions using ctDNA-MRD assessment, similar to the existing Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma 3.2024 guidelines (CLL-E, page 2 of 2).

Specifically, we request that the guidelines describe that evidence shows that:

- Cell-free DNA MRD is superior to cellular MRD for LBCL

- ctDNA-MRD assessment using Foresight CLARITY has demonstrated prognostic performance superior to PET-CT at a LOD95 of 1e-6, and increased analytical sensitivity leads to better clinical performance of MRD in LBCL

- Foresight’s MRD test with a high-level description that ctDNA-MRD negative is associated with low risk of recurrence and that ctDNA-MRD positive is associated with a high risk of recurrence regardless of PET-CT result. In the case of discordant ctDNA-MRD and PET results, short interval surveillance is appropriate to increase monitoring given the increased risk of disease.

In addition, we request that this inclusion be specific to Foresight’s MRD test based on the evidence available.

We request the inclusion of epcoritamab-bysp in combination with GemOx in the NCCN B-Cell Lymphomas Guidelines as a category 2A recommendation for the below section:

BCEL-C, 2 of 6: Diffuse Large B-Cell Lymphoma Second-line, No Intention to Proceed to Transplant, Preferred Regimen

We request the inclusion of epcoritamab-bysp in combination with R-DHAX/C in the NCCN B-Cell Lymphoma Guidelines as category 2A recommendations for the below sections:  

BCEL-C, 2 of 6: Diffuse Large B-cell Lymphoma

Second-line, intention to proceed to transplant, preferred

Second-line, relapsed disease <12 months or primary refractory disease

For plasmablastic lymphoma, consider the inclusion of bentuximab vedotin for relapsed disease.