Abstract
Background: Peripheral T-cell lymphoma (PTCL) is a group of aggressive non-Hodgkin's lymphomas (NHL) with high heterogeneity. The first-line treatment commonly used for firstly-diagnosed PTCL is the CHOP-like regimen. However, in addition to ALK+ALCL, these regimens present poor long-term survival rate in other subtypes, mostly less than 30-40%. Even with the consolidation of autologous hematopoietic stem cell transplantation, studies have reported that the 5-year overall survival rate is barely about 50%. Therefore, for PTCL patients who have achieved remission and undergone autologous hematopoietic stem cell transplantation, there is an urgent need to explore a maintenance treatment strategy. Chidamide is an oral type of selective HDAC inhibitor with subtype specificity for HDAC 1, 2, 3, and 10. It has a regulatory effect on abnormal epigenetic functions of tumors and a novel induction and activation of cellular immune function. In China, it has been approved for relapsed or refractory PTCL at a dose of 30 mg/time, twice a week. The study of chidamide has proved its satisfactory efficacy and safety characteristics for PTCL again. This study preliminarily evaluates the near term effects of chidamide combined with chemotherapy in the first-line treatment and maintenance value of PTCL through retrospective analysis.
Methods: We collect adult peripheral T-cell lymphomas inducing by CHOP-like regimen with chidamide or not. The complete response rate (CR), objective response rate (ORR), progression-free survival time (PFS) and overall survival time (OS) of patients in the combined chidamide group and non-combined group were separately analyzed and evaluated. Meanwhile, the OS in the chidamide-maintenance and non-chidamide maintenance of the PTCLs were also brought to study.
Results: A total of 82 patients recruited, with a median age of 60 years (14-79 years), including 45 peripheral T-cell lymphoma (PTCL-NOS), 23 angioimmunoblastic lymphoma (AITL), 14 anaplastic large cell lymphoma (ALCL), and the follow-up time cutoff was April 30, 2021. Among 82 patients, 39 patients were treated with chidamide+CHOP-like as the first-line treatment, and 43 patients were treated with CHOP-like as the first-line treatment. The CR rate of the first-line combined chidamide group was 62%, and the ORR was 87%. The CR rate of the first-line non-combined chidamide group was 42% and the ORR was 74%. There was no significant difference in CR rate and ORR between the two groups, but the CR rate has potential clinical benefits. The median PFS of the combined chidamide group was longer than that of the non-combined group by 8 months (18.9m VS 10.9m), but there was no significant statistical difference (p=0.255). Among 82 patients, regardless of first-line treatment or salvage treatment, 42 patients in the maintenance treatment group of chidamide did not reach the median OS, and the median OS of 40 patients in the non-maintenance group was 18.9 months. The difference between the groups was statistically significant (p <0.001). There were totally 66 patients responding to the first-line treatment (CR+PR). 8 patients with sequential autologous stem cell transplantation (ASCT), 34 patients with chidamide maintenance treatment, and both groups didn't reach the median OS. The third group including 24 patients who did not undergo ASCT or chidamine maintenance presenting a median OS of 45.5 months. However, due to the limitation of follow-up time, the difference between the groups was not statistically significant, but the first two groups showed a trend of clinical benefit, which requires further follow-up. During the follow-up period, 48 patients had disease progression with first-line treatment, 23 patients had disease progression using combined chidamide as salvage treatment, and 25 patients in the non-combined chidamide group suffered disease progression. There was a statistically significant difference in OS between the groups (mOS: less than 11.8 months of VS, p =0.03). Subgroup analysis showed that chidamide maintenance treatment in the PTCL-NOS group provided a significant improvement in the prognosis (mOS: 21m VS 5.6m).
Conclusion: It preliminarily suggested that chidamide maintenance therapy for PTCL provided an ideal survival benefit, especially In patients with PTCL-NOS subtypes. First-line treatment combined with chidamide and chidamide maintenance therapy may improve the poor survival prognosis.
No relevant conflicts of interest to declare.
