Multiple Myeloma Adult Patient

Patient Highlights

Myeloma patient with high-risk cytogenetics (17p deletion) and renal comorbidities
Patient achieved sCR following induction and proceeded to autologous stem cell transplant
Following transplant, maintenance was initiated
clonoSEQ Tracking (MRD) test employed for routine monitoring and eventually used to inform recommendation to re-initiate therapy

Patient History

Renal failure on dialysis
Diagnosed with multiple myeloma; genomic analysis revealed 17p deletion
Achieved stringent CR following 6 cycles of CyBorD induction
Proceeded to autologous stem cell transplant and then began RVD maintenance

Physician's Perspective

“The typical pattern with high-risk patients is that they respond very quickly but also relapse very fast. In the case of this patient, we used triplet therapy (RVD) in maintenance, but the patient pressed to stop treatment because he didn’t like the side effects. He dropped dexamethasone and then lenalidomide over the course of 2016. In May 2017, he decided to stop bortezomib as well. I was concerned and negotiated with him to try an oral targeted therapy. Three months later, he had a clonoSEQ MRD-positive result of 4 residual cells per million. At that point, having seen many other patients with low-level MRD go on to relapse, I recommended that the patient go back on triplet therapy.

If a patient insists on stopping therapy, we watch them more carefully. An MRD+ result becomes a way to motivate the patient to get back on therapy. In some cases, I might watch the MRD over time, but this patient had such bad-risk disease that I wanted to re-start treatment immediately. In every situation where I’ve seen MRD going up, they all relapsed eventually.”*

*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

At diagnosis, the clonoSEQ Clonality (ID) Test detected considerable disease burden. Patient was started on a CyBorD induction regimen.
In July 2014, post-induction clonoSEQ Tracking (MRD) Test results found no evidence of measurable residual disease (MRD) in the bone marrow. Patient proceeded to transplant in September 2014.
Post-transplant (six months later), a clonoSEQ Tracking (MRD) test showed that MRD negativity was maintained during the patient’s first three months of maintenance therapy.
Patient’s maintenance regimen was continued, and two routine clonoSEQ Tracking (MRD) tests conducted 12 months and 22 months later continued to show MRD-negative results. In May 2017, patient elected to discontinue all therapy.
In October 2017, clonoSEQ detected 4 cells per million. Due to high-risk status, physician recommended immediate re-initiation of triplet therapy.

*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.