Monitoring MRD Can Help Diagnose Cutaneous T-Cell Lymphoma

Researchers were able to use a next-generation sequencing assay to not only monitor minimal residual disease (MRD), but also to confirm diagnosis of cutaneous T-cell lymphoma, which can present as more benign conditions early on.

Minimal residual disease (MRD) can be used as a prognostic factor for survival outcomes in patients with certain cancers; however, there are various methods being used to assess MRD.

In a new study published in Archives of Pathology & Laboratory Medicine, researchers from Moffitt Cancer Center were able to use the clonoSEQ Assay in routine clinical practice for 2 years to assess patients with lymphoid and plasma cell malignancies and confirm diagnosis of cutaneous T-cell lymphoma (CTCL). The assay uses multiplex polymerase chain reaction (PCR) and next-generation sequencing (NGS).

“Making a timely, accurate diagnosis of CTCL is challenging as initial presentation may mimic benign skin dyscrasias such as atopic dermatitis and psoriasis, and the most common clinical test, TCR-γ PCR, has a high false-negative rate,” the authors explained.

They used clinical samples for clonality assessment (ID) from patients with suspected CTCL and analyzed them for the presence of T-cell receptor (TCR) clonal populations. A total of 390 patients provided at least 1 ID sample for a total of 431 ID and 335 MRD samples. The majority of patients had multiple myeloma (n = 192), while only 66 patients had suspected CTCL.

The 2 most common sources of ID samples were formalin-fixed, paraffin-embedded bone slides of tissue from bone marrow and fresh bone marrow slides, and the most common sources of MRD samples were fresh bone marrow and peripheral blood. Of the MRD samples, 77.2% of fresh bone marrow and 58.3% of peripheral blood were MRD positive.

More than half (59.7%) of the 766 samples with evaluable data were initiated with the assay in less than a day. From the 66 patients with suspected CTCL, 95 ID samples were analyzed and the dominant TCR-ß and/or TCR-γ clonotypes were identify in 42.1%, confirming the diagnosis of CTCL.

The authors noted that the clonoSEQ NGS-MRD assay has several advantages over previous techniques when it came to assessing MRD. Traditionally, Moffitt has used flow cytometry or B- or T-cell gene rearrangements to assess residual disease. However, flow cytometry “is technically challenging” and “interpretation of the results is subject.” In addition, B- and T-cell gene rearrangements are limited by pseudoclonality and “subjectivity in the interpretation of differentiation between clonal and nonclonal peaks.”

In comparison, the NGS-MRD assay was more sensitive and “can routinely detect 1 tumor cell in 106 healthy cells,” which makes the MRD detection more accurate with lower tumor burden. The authors added that the assay “has informed clinical decision making.” For instance, MRD negativity has been used to discontinue therapy when there are significant toxicities. MRD positivity has also been used to make decisions on the use of stem cell transplant and conditioning regimen intensity, the authors explained.

The results of this 2-year study demonstrate the “value of the NGS assay in the differential diagnosis of CTCL,” they added. However, there were challenges, including initially low calibration rates and the lack of awareness among pathologists of the value of MRD testing in this patient population.

“The development and implementation of this standardized, robust, and objective methodology to assess MRD status will aid the exploration of personalized therapeutic approaches and holds the potential of improving outcomes in patients with lymphoid malignancies,” the authors concluded.

Reference

Hussaini MO, Srivastave J, Wee Lee L, et al. Assessment of clonotypic rearrangements and minimal residual disease in lymphoid malignancies: a large cancer center experience using clonoSEQ. Arch Pathol Lab Med. Published online August 3, 2021. doi:10.5858/arpa.2020-0457-OA