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Frontiers in Medicine 2021Peripheral T-cell lymphoma (PTCL) is an extensive class of biologically and clinically heterogeneous diseases with dismal outcomes. The histone deacetylase inhibitor...
Peripheral T-cell lymphoma (PTCL) is an extensive class of biologically and clinically heterogeneous diseases with dismal outcomes. The histone deacetylase inhibitor (HDACi) romidepsin was approved for relapsed and refractory (R/R-PTCL) in 2011. This meta-analysis was performed to assess the efficacy and safety of romidepsin in PTCL. We searched for articles on the HDAC inhibitor romidepsin in the treatment of PTCL in Embase, Web of Science, and PubMed. The methodology is further detailed in PROSPERO (CRD42020213651, CRD42020213553). The 2-year overall survival (OS), 2-year progression-free survival (PFS), and their corresponding to 95% confidence intervals (CIs) were measured. Besides, corresponding 95% CIs were pooled for the complete response (CR), partial response (PR), duration of response (DoR), and risk of adverse events (AEs). Eleven studies containing 388 patients were incorporated into the quantitative synthesis, of which R/R-PTCL patients were the dominant portion, accounting for 94.3% (366/388). For all studies, the CR rate was 20% (95% CI, 13-27%, random effects model), and the PR rate was 18% (95% CI, 12-25%, random effects model). The 2-year OS was 48% (95% CI, 38-59%, fixed effects model), and the 2-year PFS was 17% (95% CI, 13-21%, fixed effects model). There were no significant differences between romidepsin monotherapy and romidepsin plus additional drugs. Hematological toxicities, such as lymphopenia and granulocytopenia, remained the most continually happening grade 3 or higher AEs, accounting for 46 and 28%, respectively. None of the studies reported any drug-related mortality. Considering that most of the included patients had R/R-PTCL, the addition of romidepsin significantly enhance the efficacy. And AEs were tolerable as the grade 3/4 AEs in romidepsin monotherapy was 7% (95% CI, 6-8%). It is imperative to further expand the first-line application of romidepsin and carry out personalized therapy based on epigenomics, which will improve the survival of PTCL patients. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213651 and https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213553.
PubMed: 34805202
DOI: 10.3389/fmed.2021.732727 -
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 -
Journal of Virus Eradication Sep 2023Understanding the clinical potency of latency-reversing agents (LRAs) on the HIV-1 reservoir is useful to deploy future strategies. This systematic review evaluated the... (Review)
Review
INTRODUCTION
Understanding the clinical potency of latency-reversing agents (LRAs) on the HIV-1 reservoir is useful to deploy future strategies. This systematic review evaluated the effects of LRAs in human intervention studies.
METHODS
A literature search was performed using medical databases focusing on studies with adults living with HIV-1 receiving LRAs. Eligibility criteria required participants from prospective clinical studies, a studied compound hypothesised as LRA, and reactivation or tolerability assessments. Relevant demographical data, LRA reactivation capacity, reservoir size, and adverse events were extracted. A study quality assessment with analysis of bias was performed by RoB 2 and ROBINS-I tools. The primary endpoints were HIV-1 reservoir reactivation after LRA treatment quantified by cell-associated unspliced HIV-1 RNA, and LRA tolerability defined by adverse events. Secondary outcomes were reservoir size and the effect of LRAs on analytical treatment interruption (ATI) duration.
RESULTS
After excluding duplicates, 5182 publications were screened. In total 45 publications fulfilled eligibility criteria including 26 intervention studies and 16 randomised trials. The risk of bias was evaluated as high. Chromatin modulators were the main investigated LRA class in 24 studies. Participants were mostly males (90.1%). Where reported, HIV-1 subtype B was most frequently observed. Reactivation after LRA treatment occurred in 78% of studies and was observed with nearly all chromatin modulators. When measured, reactivation mostly occurred within 24 h after treatment initiation. Combination LRA strategies have been infrequently studied and were without synergistic reactivation. Adverse events, where reported, were mostly low grade, yet occurred frequently. Seven studies had individuals who discontinued LRAs for related adverse events. The reservoir size was assessed by HIV-1 DNA in 80% of studies. A small decrease in reservoir was observed in three studies on immune checkpoint inhibitors and the histone deacetylase inhibitors romidepsin and chidamide. No clear effect of LRAs on ATI duration was observed.
CONCLUSION
This systematic review provides a summary of the reactivation of LRAs used in current clinical trials whilst highlighting the importance of pharmacovigilance. Highly heterogeneous study designs and underrepresentation of relevant patient groups are to be considered when interpreting these results. The observed reactivation did not lead to cure or a significant reduction in the size of the reservoir. Finding more effective LRAs by including well-designed studies are needed to define the required reactivation level to reduce the HIV-1 reservoir.
PubMed: 37663575
DOI: 10.1016/j.jve.2023.100342