Track: Clinical Studies

Topic: Lymphoproliferative Disorders

Abstract:

We recently found that TRBC1 immunohistochemistry (IHC) can detect persistent/residual cutaneous T-cell lymphoma (CTCL) in mogamulizumab-associated rash (MAR), when the tumor burden identified by high-throughput sequencing (HTS) of T-cell receptor (TCR) genes is relatively large. Here, we postulate that tissue flow cytometry (FC) can also be used to detect persistent/residual tumor in MAR while providing insight into heterogeneity of tumor and reactive infiltrates post-mogamalizumab.

MAR biopsies were analyzed by FC for abnormal T-cell populations. Non-neoplastic cells were evaluated by FC for CD4/CD8 predominance. TRBC1-IHC was assessed on concurrent biopsies from the same clinical site; TRBC1 expression in ≥70% or ≤25% was considered TRBC1-restricted/clonal.

16 MAR biopsies from 10 patients were evaluated by FC; an abnormal T-cell population was detected in 9/16. TRBC1-IHC was assessed in 14 concurrent biopsies from 9 patients; 6/14 were clonal, all of which revealed an abnormal T-cell population by FC. Among 8 biopsies non-clonal by TRBC1-IHC, FC showed an abnormal T-cell population in two. FC analysis of reactive/non-neoplastic T cells revealed CD4CD8 in 2 with abnormal/clonal T-cell populations and 2 non-clonal cases.

Compared to TRBC1-IHC, tissue FC more often detected an abnormal/clonal T-cell population in MAR, suggesting utility in assessment of persistent/residual CTCL for clinical decision-making. As second/unrelated clones may be present, tracking phenotypic aberrancies, TCR-Vβ analysis, and/or TRBC1 restriction of previously identified tumor clones with multiparameter FC is crucial. Further study is needed to determine the clinical significance of FC-detected low-levels of persistent/residual CTCL and variations in reactive immune infiltrates in MAR.

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Rachel Christensen, MD