Association of a Dominant T-Cell Clone in Peripheral Blood With Time to Systemic Treatment in Patients With Stage IB Mycosis Fungoides

Patients with early-stage mycosis fungoides (MF) generally receive skin-directed therapies (SDT) as initial treatment; however, a proportion will experience failure of SDT and require systemic therapy, alone or in combination with SDT, without developing extracutaneous disease. Studies^1,2 have found that 12% to 35% of patients with early-stage MF had a dominant T-cell receptor (TCR) clone in the blood that was associated with disease progression and shorter survival. We hypothesized that a peripheral TCR clone may represent circulating malignant cells that are not affected by SDT and therefore serve as a reservoir of tumor cells that can replenish those in the skin previously eradicated by SDT, thus increasing the risk of SDT failure. We investigated whether, in patients with early MF, detection of a peripheral TCR clone was associated with inadequate response to SDT and a shorter time to systemic treatment (TTST), without developing extracutaneous disease.

In this cohort study, the cutaneous lymphoma database of the University of California, San Francisco (range, May 20, 2010, to January 20, 2021), was searched for adults with a clinicopathologic diagnosis of stage IB MF who received SDT alone as first-line treatment (including topical agents, narrow-band UV-B therapy, and psoralen and UV-A) and were followed up for at least 6 months. T-cell receptor clonality was assessed by BIOMED-2 primer polymerase chain reaction assays (Invivoscribe Inc). A positive peripheral clone was defined as the presence of a dominant TCRβ, TCRγ, or both. The primary end point was TTST, defined as median (SE) time from diagnosis to initiation of first systemic treatment resulting from inadequate response to SDT without development of extracutaneous disease, assessed by the treating physicians. Secondary end points were time to advanced-stage progression and overall survival. End points were summarized by Kaplan-Meier curves and compared using the log-rank test. The Wald test was used to compare cumulative incidence of requiring systemic treatment at 12 and 36 months. A 2-tailed P < .05 was considered statistically significant. This study was approved by the University of California, San Francisco, Institutional Review Board, which waived informed consent because of the use of deidentified data. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

We identified 47 consecutive patients with stage IB MF (1 with MF/lymphomatoid papulosis overlap) who met the inclusion criteria, with 8 missing TCR status. Among 39 patients with peripheral TCR status, 17 (43.6%) had clone positivity (Table). With a median (SE) follow-up of 36.2 (29.4) months, patients with a positive clone experienced significantly shorter TTST, with a median TTST of 61.4 (18.5) months vs not reached (log-rank P = .01) in patients with vs without a clone (Figure). Cumulative incidences of systemic treatment in patients with vs without a clone were 29.4% vs 4.5% (P = .06) at 12 months and 35.3% vs 9.1% (P = .07) at 36 months. There were no differences in overall survival or in the probability of higher stage progression between the 2 groups.

This cohort study found that 43.6% of patients with stage IB MF had a peripheral TCR clone, consistent with a previous report³ of 35% in patients with stage T2 disease. Furthermore, a peripheral TCR clone was associated with a shorter TTST due to inadequate response to SDT.

The study’s limitations include its retrospective design; the inability to compare synchronous vs asynchronous clonality; and the small study population, which does not allow us to assess whether early use of systemic therapy can impact outcome. To our knowledge, this is the first study to report the association between TCR clonality in the blood and TTST. These results suggest that early use of systemic therapy in patients with skin-only disease and a circulating clone may result in improved treatment response and longer treatment-free time. The results may also help practitioners personalize management of early-stage MF and allow them to better provide anticipatory guidance to patients.

Accepted for Publication: April 21, 2022.

Published Online: June 22, 2022. doi:10.1001/jamadermatol.2022.2100

Corresponding Author: Weiyun Z. Ai, Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, 400 Parnassus Ave, 4th Floor, San Francisco, CA 94143 (Weiyun.Ai@ucsf.edu).

Author Contributions: Drs Ai and Raychaudhuri had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Raychaudhuri and Charli-Joseph contributed equally to this work.

Concept and design: Raychaudhuri, Charli-Joseph, Pincus, Ai.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Raychaudhuri, Charli-Joseph, Huang, Ai.

Critical revision of the manuscript for important intellectual content: Raychaudhuri, Mintz, Pincus, Ai.

Statistical analysis: Raychaudhuri, Charli-Joseph, Huang, Ai.

Obtained funding: Ai.

Administrative, technical, or material support: Raychaudhuri, Mintz.

Supervision: Pincus, Ai.

Conflict of Interest Disclosures: Dr Ai reported receiving honoraria from Kymera Therapeutics, BeiGene, ADC Therapeutics, Kite Pharma, Acrotech Biopharma, Nurix Therapeutics, Seagen, and Walking Fish Therapeutics outside the submitted work. No other disclosures were reported.

Funding/Support: This research was supported by the Donna L. and Edward E. Martins Foundation and by James Gassel during the conduct of the study.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We wish to thank Mark Moasser, MD, Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, for his critical review of the manuscript and Aisling Storey, Department of Dermatology, University of California, San Francisco, for administrative assistance. They were not compensated for this work.