Chronic Lymphocytic Leukemia Adult Patient

Patient Highlights

High-risk CLL patient monitored post-transplant with clonoSEQ Tracking (MRD) Test using peripheral blood samples
Due to slowly declining, but still present MRD, the patient was started on ibrutinib
Regular peripheral blood MRD testing was used to monitor disease course

Patient History

Early 70s male with high-risk, 17p deletion chronic lymphocytic leukemia (CLL).
Patient underwent autologous stem cell transplant in November 2015.
Post-transplant, the patient began ibrutinib maintenance after transplant did not result in measurable residual disease (MRD) negativity.

Physician's Perspective

“Post transplant, my practice is to give patients a year to become MRD-negative. This patient was slow to become MRD-negative, so I decided to add additional therapy with ibrutinib.¹ After adding ibrutinib, the patient’s MRD continued to be monitored by clonoSEQ every 3 months using peripheral blood samples.”*

*Clinician has received equity compensation as a member of Adaptive’s Scientific Advisory Board. Clinician’s research has also been supported, in part, via product grants.

Use of the clonoSEQ Assay

Physician sent a blood sample for clonoSEQ Clonality (ID) Test in preparation for subsequent peripheral blood MRD monitoring post-transplant.
Continuous clonoSEQ Tracking (MRD) Tests showed that the patient’s MRD slowly declined post-transaplant.
In June 2016, a year and a half after transplant, the patient was started on ibrutinib as the patient did not achieve MRD-negativity.1
After adding ibrutinib, the patient’s MRD continued to decline. Subsequent MRD monitoring with the clonoSEQ Tracking (MRD) Test will continue every three months utilizing peripheral blood samples.

*This case study was based off results generated from an earlier version of the clonoSEQ Assay.

1. Ryan C, et al. Blood. 2016;128(25):2899-2908.

Intended Use:

The clonoSEQ Assay is an in vitro diagnostic that uses multiplex polymerase chain reaction (PCR) and next-generation sequencing (NGS) to identify and quantify rearranged IgH (VDJ), IgH (DJ), IgK and IgL receptor gene sequences, as well as translocated BCL1/IgH (J) and BCL2/IgH (J) sequences in DNA extracted from bone marrow from patients with B-cell acute lymphoblastic leukemia (ALL) or multiple myeloma (MM), and blood or bone marrow from patients with chronic lymphocytic leukemia (CLL).

The clonoSEQ Assay measures minimal residual disease (MRD) to monitor changes in burden of disease during and after treatment. The test is indicated for use by qualified healthcare professionals in accordance with professional guidelines for clinical decision-making and in conjunction with other clinicopathological features.

The clonoSEQ Assay is a single-site assay performed at Adaptive Biotechnologies Corporation in Seattle, Washington.

Special Conditions for Use:

For in vitro diagnostic use.
For prescription use only (Rx only).

Limitations:

ALL, MM, and CLL:
MRD values obtained with different assay methods may not be interchangeable due to differences in assay methods and reagent specificity. The results obtained from this assay should always be used in combination with the clinical examination, patient medical history, and other findings. The clonoSEQ Assay is for use with specimens collected in EDTA tubes. Results may vary according to sample time within the course of disease or by sampling site location. The assay may overestimate MRD frequencies near the limit of detection (LoD). The MRD frequency LoD varies based on the amount of gDNA that is tested and using lower gDNA input may prevent MRD detection at low frequencies. Sample processing and cell enrichment strategies may affect the measured MRD frequency. The volume and cellularity of sampled input material may affect the ability to detect low levels of disease. False positive or false negative results may occur for reasons including, but not limited to: contamination; technical and/or biological factors such as the type of rearrangement or the size of the junction region. The assay has been validated with the Illumina NextSeq500 and 550.

For CLL:
MRD is based on measurements of tumor cells detected in peripheral blood and/or bone marrow. However, patients may have significant residual disease in unassessed compartments and U-MRD in one compartment cannot fully rule out the presence of disease in the other compartment, for example, U-MRD in blood may not be the same in bone marrow. Therefore assessment of MRD in CLL should employ a multimodal approach including clinical examination, patient medical history, and other findings. Outcome for patients with MRD detectable in bone marrow but not in peripheral blood (PB-/BM+) may differ according to type of therapy. This assay is capable of monitoring specific tumor clonotypes. The association between MRD assessments and patient clinical status for the purpose of monitoring changes in disease (e.g., relapse, remission, stable disease) has not been demonstrated. The value of MRD in CLL for previously untreated or “watch and wait” patients is not established. CLL is a heterogeneous disease. MRD values and expectations for outcome may not be generalizable across treatments. Changes in MRD should be interpreted with caution when used to evaluate disease burden in therapies that have not been validated. Regardless of MRD status, cytogenetics play an independent role in patient risk status and its impact on PFS/OS.

For important information about the FDA-cleared uses of clonoSEQ including test limitations, please visit clonoSEQ.com/technical-summary.