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|Title:||T follicular helper phenotype predicts response to histone deacetylase inhibitors in relapsed/refractory peripheral T-cell lymphoma.|
|Epworth Authors:||Prince, Miles|
|Other Authors:||Ghione, Paola|
van der Weyden, Carrie
|Keywords:||Histone Deacetylase Inhibitors (HDACi)|
Peripheral T-cell Lymphoma (PTCL)
Angioimmunoblastic T-Cell Lymphoma (AITL)
Not Otherwise Specified (NOS)
T Follicular Helper Phenotype
Histone Deacetylase Inhibitors (HDACi)
Relapsed/Refractory Peripheral T-Cell Lymphoma
T Follicular Helper (TFH) Cells
Progression-Free Survival (PFS)
Mann-Whitney U Test
Fisher’s Exact Test
Logistic Regression Model
Performance status (ECOG)
Phenotype and Gene Expression Profiling
Non-TFH phenotype PTCL
MSK IMPACT-heme 400-genes targeted sequencing
Epworth Centre for Immunotherapies and Snowdome Laboratories
Molecular Oncology and Cancer Immunology
Cancer Services Clinical Institute, Epworth HealthCare, Victoria, Australia
|Publisher:||American Society of Hematology (ASH)|
|Citation:||Blood Adv . 2020 Oct 13;4(19):4640-4647.|
|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. T follicular helper phenotype is an independent predictor of response to HDACi in peripheral T-cell lymphoma. PFS showed a trend in favor of the TFH phenotype, and 18% of the TFH patients can use HDACi as a bridge to allogeneic transplantation. In conclusion, these data suggest that using HDACi in combination therapies for AITL and TFH PTCL might be a particularly promising strategy. Likewise, when designing a trial including HDACi, the proportion of patients with TFH-phenotype PTCL may influence the overall response to that treatment.|
|Journal Title:||Blood Advances|
|Affiliated Organisations:||Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.|
Lymphoma and Myeloma Service, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Department of Hematology and Oncology, Washington University School of Medicine, St. Louis, MO.
Department of Epidemiology and Biostatistics and Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
Hematology Department, Concord Hospital, University of Sydney, Sydney, Australia.
Department of Oncology, Stanford University, Stanford CA.
Division of Oncology and Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE.
Department of Medicine, Weill Cornell Medicine, New York, NY.
Division of Cancer Medicine, Peter MacCallum Cancer Center, Parkville, Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
|Type of Clinical Study or Trial:||Clinical Trial|
|Appears in Collections:||Cancer Services|
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