Tips for using and interpreting the clonoSEQ NGS-MRD assay
| Frequently asked questions . | Expert recommendation . |
|---|---|
| Can I use NGS-MRD for my patient if I did not send a sample for ID at diagnosis? | Identification of a dominant sequence from diagnostic material is required for subsequent MRD tracking. If not sent at diagnosis, dominant sequence identification can be performed using archived unstained marrow aspirate or peripheral smear slides. Relapse samples can also be used to define dominant sequences if not done previously. |
| Can I use NGS-MRD for a patient with a lymphoblastic lymphoma presentation of ALL? | Yes, dominant sequence identification can be performed on diagnostic tissue by sending FFPE slides or scrolls. |
| The ID report resulted as “polyclonal.” What should I do? | A polyclonal result indicates that dominant clonal sequences were not identified on the specimen sent for analysis. Etiologies include (1) immature leukemia that has not undergone rearrangement; (2) sample did not contain adequate malignant cells; and (3) degraded DNA. If an alternative sample is available, it can be sent for a second attempt. TCR sequences can also be explored. |
| What does it mean when the MRD report is positive but below LOD? | This means that dominant sequence(s) were detected below the limit of sequence detection. Each dominant sequence has an individual LOD. It is important to assess the result in context with the type of sequence detected (eg, IgH vs Igκ vs Igλ), the sequence LOD, and the clinical data. Positive IgH sequences below the LOD are often true positives and should not be ignored, as they have been shown to be highly predictive of relapse after HCT and CAR T-cell therapy. Isolated positive sequences (only 1 tracking dominant sequence from the baseline sample) in which LOD is high and more specific sequences are not present warrant repeat observations over time, because they may be false positives. |
| What if a new dominant sequence emerges as I follow my patient? | During the course of therapy, expansion pressure may lead to a hematopoietic clone rising to levels that meet the definition of dominant sequence. Such clonal sequences would then be reported out as new dominant sequences. If established tracking sequences associated with disease are not present, the new dominant sequence likely does not represent disease, and may decrease or disappear with time. |
| Can I use peripheral blood to track NGS-MRD? | Although not FDA cleared for ALL, the use of peripheral blood for NGS-MRD tracking is clinically available. Studies show strong correlation between blood and marrow for NGS-MRD assessment, although marrow generally has a higher level of sensitivity. |
| I do not understand the MRD report. What should I do? | Several resources are available to help with report interpretation. It is highly advised to reach out to an expert if there are questions, particularly if clinical intervention is under consideration. Adaptive offers services for their assay to answer these types of questions. |
| Frequently asked questions . | Expert recommendation . |
|---|---|
| Can I use NGS-MRD for my patient if I did not send a sample for ID at diagnosis? | Identification of a dominant sequence from diagnostic material is required for subsequent MRD tracking. If not sent at diagnosis, dominant sequence identification can be performed using archived unstained marrow aspirate or peripheral smear slides. Relapse samples can also be used to define dominant sequences if not done previously. |
| Can I use NGS-MRD for a patient with a lymphoblastic lymphoma presentation of ALL? | Yes, dominant sequence identification can be performed on diagnostic tissue by sending FFPE slides or scrolls. |
| The ID report resulted as “polyclonal.” What should I do? | A polyclonal result indicates that dominant clonal sequences were not identified on the specimen sent for analysis. Etiologies include (1) immature leukemia that has not undergone rearrangement; (2) sample did not contain adequate malignant cells; and (3) degraded DNA. If an alternative sample is available, it can be sent for a second attempt. TCR sequences can also be explored. |
| What does it mean when the MRD report is positive but below LOD? | This means that dominant sequence(s) were detected below the limit of sequence detection. Each dominant sequence has an individual LOD. It is important to assess the result in context with the type of sequence detected (eg, IgH vs Igκ vs Igλ), the sequence LOD, and the clinical data. Positive IgH sequences below the LOD are often true positives and should not be ignored, as they have been shown to be highly predictive of relapse after HCT and CAR T-cell therapy. Isolated positive sequences (only 1 tracking dominant sequence from the baseline sample) in which LOD is high and more specific sequences are not present warrant repeat observations over time, because they may be false positives. |
| What if a new dominant sequence emerges as I follow my patient? | During the course of therapy, expansion pressure may lead to a hematopoietic clone rising to levels that meet the definition of dominant sequence. Such clonal sequences would then be reported out as new dominant sequences. If established tracking sequences associated with disease are not present, the new dominant sequence likely does not represent disease, and may decrease or disappear with time. |
| Can I use peripheral blood to track NGS-MRD? | Although not FDA cleared for ALL, the use of peripheral blood for NGS-MRD tracking is clinically available. Studies show strong correlation between blood and marrow for NGS-MRD assessment, although marrow generally has a higher level of sensitivity. |
| I do not understand the MRD report. What should I do? | Several resources are available to help with report interpretation. It is highly advised to reach out to an expert if there are questions, particularly if clinical intervention is under consideration. Adaptive offers services for their assay to answer these types of questions. |
FFPE, formalin-fixed paraffin-embedded.