Chronic Lymphocytic Leukemia Adult Patient

Patient Highlights

CLL patient with apparent response to ibrutinib showed constitutional symptoms
clonoSEQ Tracking (MRD) Test combined with CBC revealed increasing CLL cell counts despite decrease in overall lymphocyte count
Early detection of relapse by clonoSEQ Tracking (MRD) Test triggered preparation for allogeneic transplant

Patient History

Mid-50s male with 11q-deleted CLL.
Previously treated with two cycles of chemoimmunotherapy for symptoms, lymphadenopathy, and rapidly doubling white blood cell count complicated by prolonged myelosuppression.
Patient received autologous stem cell transplant in April 2016.
Patient started on ibrutinib in early September 2016.

Physician's Perspective

“Clinical studies show that patients progressing during or after ibrutinib therapy have poor outcomes.¹ This patient appeared to be doing well by traditional measures, but the presence of constitutional symptoms prompted me to start testing for measurable residual disease (MRD), which revealed that although the total lymphocyte count was down, CLL cell count was actually increasing. By catching this relapse early and taking into account other available information, we were able to intervene early. In this case donors were identified so transplant is an option. If no donors were available, we may have pursued a clinical trial.”*

*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 peripheral blood samples for clonoSEQ Clonality (ID) Test in preparation for subsequent monitoring.
Six months later, the clonoSEQ Tracking (MRD) Test showed a 3X increase in absolute CLL cell count despite ibrutinib treatment. Preparations for TLIATG allogeneic hematopoietic cell transplant in December 2015 began.
One month later, measurable residual disease (MRD) levels continued to increase, as assessed by the clonoSEQ Tracking (MRD) Test, confirming decision to proceed to transplant; ibrutinib was discontinued.
Patient received TLI-ATG allogeneic hematopoietic cell transplant in April 2016.
The peripheral blood was assessed for MRD 30, 60, and 90 days posttransplant using the clonoSEQ Tracking (MRD) Test.
MRD was still present six months post-transplant. Physician started the patient on ibrutinib.
Six months after initiation of ibrutinib no MRD detected by clonoSEQ.

1. Byrd JC, et al. Blood. 2015;125:2497-2506.

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.