Title | T follicular helper phenotype predicts response to histone deacetylase inhibitors in relapsed/refractory peripheral T-cell lymphoma. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Ghione P, Faruque P, Mehta-Shah N, Seshan V, Ozkaya N, Bhaskar S, Yeung J, Spinner MA, Lunning M, Inghirami G, Moskowitz A, Galasso N, Ganesan N, van der Weyden C, Ruan J, H Prince M, Trotman J, Advani R, Dogan A, Horwitz S |
Journal | Blood Adv |
Volume | 4 |
Issue | 19 |
Pagination | 4640-4647 |
Date Published | 2020 10 13 |
ISSN | 2473-9537 |
Keywords | Histone Deacetylase Inhibitors, Humans, Lymphoma, T-Cell, Peripheral, Neoplasm Recurrence, Local, Phenotype, Retrospective Studies, T-Lymphocytes, Helper-Inducer |
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 = .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. |
DOI | 10.1182/bloodadvances.2020002396 |
Alternate Journal | Blood Adv |
PubMed ID | 33002132 |
PubMed Central ID | PMC7556143 |
Grant List | P01 CA229100 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States P50 CA192937 / CA / NCI NIH HHS / United States |
Related Faculty:
Giorgio Inghirami, M.D.