Systemic Retinoids in Cutaneous T-Cell Lymphoma

INTRODUCTIONSystemic retinoids are ubiquitously used in cutaneous T-cell lymphoma (CTCL), often in combination with skin-directed or systemic therapies, yet their role within contemporary multimodal treatment strategies has not been comprehensively synthesized.

METHODSWe conducted a PRISMA-ScR-guided scoping review of systemic retinoids in CTCL using PubMed, Embase, Scopus, Web of Science, and the Cochrane Library through December 1, 2025. Study-level and treatment arm-level analyses characterized treatment patterns, outcomes, and reporting practices. Reported response rates were descriptively summarized after excluding case reports and case series.

RESULTSA total of 141 studies comprising 153 treatment arms and 3805 participants with CTCL were included. Bexarotene was the most frequently studied retinoid (113/153, 73.9%), and combination therapy predominated (100/153, 65.4%). Retinoids were used across the treatment continuum, most frequently in salvage settings (85/153, 55.6%). Among treatment arms with reported stage, advanced-stage disease more frequently incorporated bexarotene-containing combination regimens than early-stage disease (80.7% vs 50.0%; p = 0.017). Among 59 overall response rate (ORR) observations from observational studies and clinical trials, median reported ORR was 60.0% for combination therapy and 51.5% for monotherapy; by individual retinoid, median reported ORRs were 56.6% for bexarotene, 59.5% for acitretin, and 57.0% for isotretinoin. Durability and safety reporting remained inconsistent, with progression-free survival and grade ≥ 3 adverse events reported in only 13.1% and 32.0% of treatment arms, respectively.

CONCLUSIONSSystemic retinoids remain versatile and clinically relevant components of contemporary CTCL management. Rather than functioning primarily as standalone therapies, they are commonly incorporated into multimodal treatment strategies across disease stages and therapeutic settings, with reported clinical activity across individual agents and both monotherapy and combination approaches. Heterogeneity across studies precludes comparative efficacy conclusions and underscores the need for standardized response assessment, durability endpoints, and comprehensive safety and demographic reporting.

Abstract from PubMed