T follicular helper phenotype predicts response to histone deacetylase inhibitors in relapsed/refractory peripheral T-cell lymphoma

Paola Ghione, Promie Faruque, Neha Mehta-Shah, Venkatraman Seshan, Neval Ozkaya, Shakthi Bhaskar, James Yeung, Michael A. Spinner, Matthew Lunning, Giorgio Inghirami, Alison Moskowitz, Natasha Galasso, Nivetha Ganesan, Carrie van der Weyden, Jia Ruan, H. Miles Prince, Judith Trotman, Ranjana Advani, Ahmet Dogan, Steven Horwitz

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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 5.0035), with TFH phenotype being an independent predictor of ORR (P 5.009). 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.

Original languageEnglish
Pages (from-to)4640-4647
Number of pages8
JournalBlood Advances
Volume4
Issue number19
DOIs
StatePublished - Oct 13 2020

Fingerprint

Dive into the research topics of 'T follicular helper phenotype predicts response to histone deacetylase inhibitors in relapsed/refractory peripheral T-cell lymphoma'. Together they form a unique fingerprint.

Cite this