Acute Lymphoblastic Leukemia Adult Patient

Patient Highlights

Sensitivity of clonoSEQ MRD Assay allowed for early detection of relapse in post-transplant adult ALL patient
Physician began preparations for patient enrollment in CAR-T clinical trial

Patient History

No significant past medical history, diagnosed with precursor B-ALL (normal cytogenetics) in June 2014
No significant bone marrow response seen after initial induction (on day 14) or extended induction (day 28)
Refractory to salvage therapy with morphologic disease persisting in bone marrow, so referred for allo-transplant
Disease burden too high for immediate transplant, so patient was enrolled in a clinical trial of a CD22-targeted antibody drug conjugate
After one cycle of trial therapy patient was in morphological remission but with MRD detected by flow cytometry at 10^-3, so decision was made to proceed to transplant
Unrelated donor, ablative transplant carried out November 2014

Physician's Perspective

“When we rely on morphology alone, we are often surprised when a patient’s bone marrow looks beautiful at day 180 post-transplant and then six months later they show up with circulating blasts. For this patient, the sensitivity of the clonoSEQ MRD Assay allowed for early disease detection, providing me with time to prepare my patient and his other doctors for what would come next, which in this case was enrollment in a CAR-T cell clinical trial. When the follow-up MRD test came back positive and at a higher level (time-point 4), everything was already in place. My patient was able to move on to his next treatment while still relatively healthy and he was pleased that the latest technologies were guiding his treatment.”*

*Clinician has received compensation to participate in advisory meetings sponsored by Adaptive. Clinician’s research has also been supported, in part, via product grants.

Use of the clonoSEQ Assay

Transplant physician sent bone marrow sample for clonoSEQ Clonality (ID) Test before patient was enrolled in clinical trial so that clonoSEQ MRD tracking could be carried out post-transplant.
80 days post-transplant, patient’s bone marrow sample showed no evidence of disease by morphology or standard flow cytometry. Blood counts were normal and MRD was undetectable by clonoSEQ.
170 days post-transplant, patient’s bone marrow sample showed no evidence of disease by morphology or standard flow cytometry, but MRD was detected by clonoSEQ. Based on this result, immunosuppression was tapered off.
210 days post-transplant, patient’s bone marrow sample showed no evidence of disease by morphology or standard flow cytometry, but MRD was again detected by clonoSEQ, this time at a higher level.
The patient’s MRD level continued to rise, confirming that the patient was proceeding to clinical relapse and supporting decision to enroll in a CAR-T clinical trial. At 250 days post-transplant, increased disease burden as assessed by clonoSEQ was also detected for the first time by flow cytometry.

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

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.