Heterogeneity of treatment choice has been demonstrated both in US and non-US centers. Systemic treatment choice is currently guided by prognostic features, incorporating stage, immunophenotypic and molecular findings, and patient-specific factors such as age and comorbidities. Randomized controlled studies are uncommon, and the literature is composed predominantly of retrospective, cohort, and early-phase studies. International consensus guidelines are available; however, the lack of comparative trials means that there is no clear algorithmic approach to treatment. This review article reports on the systemic treatment options in current use for advanced CTCL, and on the possible future therapies, acknowledging that an algorithmic approach is not yet forthcoming to guide treatment prioritization.

Histone deacetylase inhibitors (HDACi) are active agents for peripheral T-cell lymphoma (PTCL). Anecdotally angioimmunoblastic T-cell lymphoma (AITL) appears to respond better than PTCL–not otherwise specified (NOS) to HDACi. The new World Health Organization classification shows that a subgroup of PTCL carries similarities in phenotype and gene expression profiling to AITL, comparable to T follicular helper (TFH) cells. The disease might behave similarly to AITL when treated with HDACi. We analyzed 127 patients with AITL or PTCL-NOS treated with HDACi at relapse as a single agent or in combination. We re-reviewed the pathology of all PTCL-NOS to identify the TFH phenotype. Patients received HDACi at relapse as a single agent in 97 cases (76%, 59 TFH, 38 non-TFH) or in combination in 30 cases (24%, 18 TFH, 12 non-TFH) including duvelisib, lenalidomide, lenalidomide plus carfilzomib, and pralatrexate. Seven PTCL-NOS had TFH phenotype; 2 PTCL-NOS were reclassified as AITL. Overall response rate (ORR) was 56.5% (28.9% complete response [CR]) in TFH and 29.4% (19.6% CR) in non-TFH phenotype patients (P = .0035), with TFH phenotype being an independent predictor of ORR (P = .009). Sixteen patients sufficiently responded to HDACi or HDACi in combination with another agent to proceed directly to allogeneic transplantation; 1 of 16 responded to donor lymphocyte infusion (12 TFH, 4 non-TFH). Our results, although retrospective, support that HDACi, as a single agent or in combination, may have superior activity in TFH-PTCL compared with non-TFH PTCL. This differential efficacy could help inform subtype-specific therapy and guide interpretation of HDACi trials.

Gao et al report that early use of extracorporeal photopheresis improves time to next treatment and survival in patients with Sézary syndrome.