-
Cancer Management and Research 2018Peripheral T-cell lymphomas (PTCLs) are an aggressive and diverse group of lymphomas with a T-cell origin. Most patients progress following initial treatment and require... (Review)
Review
Peripheral T-cell lymphomas (PTCLs) are an aggressive and diverse group of lymphomas with a T-cell origin. Most patients progress following initial treatment and require salvage therapy. The burden of symptoms is high due to its extra-nodal presentation, high rate of advanced disease, and associated cytopenias combined with its predilection for an elderly population. The disease is generally incurable at relapse in the absence of transplantation and treatment is aimed at prolonging life and reducing disease-related symptoms. Belinostat is a histone deacetylate inhibitor that was granted accelerated approval by the US Food and Drug Administration on July 3, 2014, for the treatment of relapsed PTCL. Here, a systemic review was conducted to assess the safety and efficacy of belinostat. A safety analysis involved 512 patients with relapsed malignancies, and an efficacy analysis focused on patients with relapsed PTCL and included a total of 144 patients. Common adverse events were noted including fatigue (35%), nausea (42.8%), and vomiting (28.5%), but comparatively low rates of grade 3/4 hematologic toxicity overall (6.4%). Efficacy analysis demonstrated an overall response rate of 25.7% and complete responses of 10.4% with the majority of discontinuations occurring for lack of efficacy. Ultimately, these results demonstrate that belinostat has comparable efficacy to other agents used in this setting and is well tolerated in regard to hematologic events, but there is limited data on patient-reported outcomes, reduction in disease-related symptoms, or quality of life.
PubMed: 30584367
DOI: 10.2147/CMAR.S149241 -
Frontiers in Oncology 2023The overall survival of peripheral T-cell lymphoma (PTCL) is dismal. Histone deacetylase (HDAC) inhibitors have exhibited promising treatment outcomes for PTCL patients....
BACKGROUND
The overall survival of peripheral T-cell lymphoma (PTCL) is dismal. Histone deacetylase (HDAC) inhibitors have exhibited promising treatment outcomes for PTCL patients. Therefore, this work aims to systematically evaluate the treatment outcome and safety profile of HDAC inhibitor-based treatment for untreated and relapsed/refractory (R/R) PTCL patients.
METHODS
The prospective clinical trials of HDAC inhibitors for the treatment of PTCL were searched on the Web of Science, PubMed, Embase, ClinicalTrials.gov, and Cochrane Library database. The pooled overall response rate, complete response (CR) rate, and partial response rate were measured. The risk of adverse events was evaluated. Moreover, the subgroup analysis was utilized to assess the efficacy among different HDAC inhibitors and efficacy in different PTCL subtypes.
RESULTS
For untreated PTCL, 502 patients in seven studies were involved, and the pooled CR rate was 44% (95% , 39-48%). For R/R PTCL patients, there were 16 studies included, and the CR rate was 14% (95% , 11-16%). The HDAC inhibitor-based combination therapy exhibited better efficacy when compared with HDAC inhibitor monotherapy for R/R PTCL patients ( = 0.02). In addition, the pooled CR rate was 17% (95% , 13-22%), 10% (95% , 5-15%), and 10% (95% , 5-15%) in the romidepsin, belinostat, and chidamide monotherapy subgroups, respectively. In the R/R angioimmunoblastic T-cell lymphoma subgroup, the pooled ORR was 44% (95% , 35-53%), higher than other subtypes. A total of 18 studies were involved in the safety assessment of treatment-related adverse events. Thrombocytopenia and nausea were the most common hematological and non-hematological adverse events, respectively.
CONCLUSION
This meta-analysis demonstrated that HDAC inhibitors were effective treatment options for untreated and R/R PTCL patients. The combination of HDAC inhibitor and chemotherapy exhibited superior efficacy to HDAC inhibitor monotherapy in the R/R PTCL setting. Additionally, HDAC inhibitor-based therapy had higher efficacy in angioimmunoblastic T-cell lymphoma patients than that in other subtypes.
PubMed: 37384289
DOI: 10.3389/fonc.2023.1127112