Characterizing Outcomes in Visceral Cutaneous T-Cell Lymphoma: A Real-World Retrospective Study

Introduction: Visceral Cutaneous T-Cell Lymphoma (vCTCL) is a rare and understudied complication of CTCL. Visceral involvement is associated with a poor prognosis, with a median survival of less than 1.5 years. We aimed to assess clinical characteristics, treatment, and outcomes associated with vCTCL.

Methods: We conducted a retrospective review of patients with vCTCL from a CTCL database of 656 patients seen at the Winship Cancer Institute at Emory University from 1990-2022. vCTCL was defined as stage 4B or M1 disease that was pathologically confirmed or clinically suspected. Clinical data collected from the electronic medical record included baseline demographics, disease characteristics, pathologic characteristics, laboratory values, and treatment patterns. Descriptive analysis was performed for covariates. Clinical outcomes were measured as overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method and univariable Cox regression analysis. Statistical analysis was performed using SAS with significance at the 0.05 level.

Results: Twenty-six patients had vCTCL of which 42.3% were black and 57.7% were white. There was an even distribution among male (53.8%) and female patients (46.2%) [Table 1]. Median age at diagnosis of vCTCL was 58.5 years (47-66). Eight patients (30.8%) had ECOG PS ≥2. The most common diagnosis was mycosis fungoides (73.1%) and Sézary syndrome (11.5%), others being primary cutaneous anaplastic large cell (n=1), cytotoxic T cell (n=1), and gamma-delta T cell lymphoma variants (n=1). At the time of initial diagnosis, TNMB stage was 1B in 7 patients (33.3%), 2A/2B in 6 (28.6%), 3A in 2 (9.5%), 4A1/A2 in 4 (19%), and 4B in 7 (33.3%). Four patients (15.4%) had N2 involvement and 8 patients (30.8%) had N3 involvement. Eight patients had stage B2 disease (30.8%). Approximately half of the cohort had large cell transformation (LCT) with 61.5% having concurrent biopsy-proven LCT with visceral metastasis. Eleven patients (60%) had matched skin and blood TCR positivity. Twenty-three patients had biopsy-proven vCTCL with the most common sites being lung (42.3%), liver (19.2%), bone marrow (11.5%), and CNS (11.5%). Nine patients (34.6%) had at least 2 sites of metastases. Liver metastases were associated with a higher rate of subsequent disease progression (HR 3.29, p=0.031). Other metastases (23%) involving the thyroid, kidney, pleural or peritoneal compartments were associated with decreased survival (HR 8.91, p<0.001) and progression (HR 4.28, p=0.009).

Median follow-up was 28.4 months (mo). The median time to visceral involvement from diagnosis was approximately 1 year. Nearly all patients (96.2%) received treatments after vCTCL diagnosis. Median time to first treatment of vCTCL was 2.3mo. Median number of systemic therapies after vCTCL diagnosis was 2. Two patients had complete response (7.7%) and one had partial response (3.8%) with the rest having progressive disease (88.5%). There was no difference in OS or PFS by race, and black patients had a trend toward improved outcomes. Median OS in black and white patients was 18.2mo and 11.4mo respectively (HR 0.5, p = 0.097, Figure 1). Median PFS in black and white patients was 8.7mo and 4.3mo respectively. Black patients had higher median lactate dehydrogenase levels at vCTCL diagnosis (p=0.018) and trended towards an earlier age at diagnosis (54 years vs 62 years) and a shorter time to metastasis (7.9mo vs. 13.3mo) but these factors were not associated with survival outcomes.

Most patients received multi-agent chemotherapy (n=13), total electron beam therapy (n=11), and brentuximab vedotin (n=6). Black and white patients had similar time to first treatment and total number of treatments. White patients were more likely to receive combination chemotherapy (66.7% vs 27.3%, p=0.047). Two patients in our cohort had durable complete response to therapy. The first patient developed CNS metastases and achieved durable response with HD-MTX. The second patient had concurrent pulmonary vCTCL and LCT and developed durable response with allogeneic transplantation. Treatments, other demographic information, ECOG, histopathology, LCT were not associated with survival outcomes.

Conclusions: Our analysis of a large CTCL cohort from a 30-year period confirms the rarity and poor outcomes in patients with visceral CTCL disease. More prospective studies and clinical trials are needed to guide treatment.

Lechowicz:ADC Therapeutics: Consultancy; Kyowa Kirin: Consultancy; EUSA Pharma: Consultancy; Secura Bio Inc: Consultancy. Allen:Daiichi Sanyko: Consultancy, Honoraria; Kyowa: Consultancy, Honoraria.