Chi-GVM Regimen for the Treatment of R/R PTCL

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of lymphoproliferative diseases caused by mature T cells, accounting for approximately 10% of non-Hodgkin lymphomas (NHL). Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) is the most common subtype, accounting for approximately 26%. This was followed by angioimmunoblastic T-cell lymphoma (AITL; 19%), anaplastic large cell lymphoma (ALCL, ALK)-positive (7%), ALK-negative (6%), and enteropathy-associated T-cell lymphoma ( EATL) . PTCLs have a worse prognosis than aggressive B-cell lymphomas; they are less responsive to standard anthracycline-based chemotherapy regimens and responses are less durable. In an analysis of 341 patients with newly diagnosed PTCL who received anthracycline chemotherapy, 3-year PFS and OS rates were 32% and 52%, respectively, significantly inferior to matched patients with diffuse large B-cell lymphoma (DLBCL).And patients who received consolidative hematopoietic cell transplantation (HCT) had no significant benefit. The prognosis of relapsed/refractory (R/R) patients is even worse. Among the 420 evaluable R/R PTCL patients in the COMPLETE registration study, the median OS of R/R patients were 29 months and 12 months respectively . There is still no effective second-line regimen that can improve patient survival, so treatment options urgently need to be optimized. Histone deacetylase (HDAC) inhibitors such as belinostat, romidepsin, etc. have been confirmed to show good efficacy in R/R AITL;Chinise original drug Chidamide is mainly targeted at Class I HDAC inhibitors (HDACi) of HDAC subtypes 1, 2, and 3 and class IIb subtype 10 have the regulatory effect on abnormal epigenetic functions of tumors. It triggers chromatin remodeling by inhibiting related HDAC isoforms to increase the acetylation level of chromatin histones, resulting in changes in gene expression (ie, epigenetic changes) targeting multiple signaling pathways, thereby inhibiting tumor cells cycle, induce apoptosis of tumor cells, and at the same time have overall regulatory activity on cellular immunity, inducing and enhancing the tumor killing effect mediated by natural killer cells (NK) and antigen-specific cytotoxic T cells (CTL). Chidamide also induces tumor stem cell differentiation and reverses the epithelial-mesenchymal phenotypic transition (EMT) of tumor cells through epigenetic regulation mechanisms, thereby restoring the sensitivity of drug-resistant tumor cells to drugs and inhibiting tumor metastasis. play a potential role in recurrence and other aspects. The above unique mechanism of action characteristics lay the foundation for the combined application of chidamide and other chemotherapy drugs in tumor treatment. Its phase II clinical study explored the effectiveness and safety of chidamide monotherapy in patients with R/R PTCL. The objective response rate (ORR) assessed by the investigators was 29.1%, and the median duration of response (DOR) was 9.9 months, and is well tolerated.Chidamide has been included in the medical insurance indications for patients with relapsed or refractory PTCL who have received at least one systemic chemotherapy in the past. However, single drug is still not effective in patients with nTFHL and needs to be combined with other drugs. Gemcitabine, dexamethasone, and cisplatin (GDP) combined with autologous hematopoietic stem cell transplantation (ASCT) can effectively treat patients with R/R PTCL, with an ORR of 72% to 80% and a CR of 47% to 48%. Among patients who subsequently underwent ASCT, 2-year post-transplant OS was 53%. A retrospective analysis showed that the gemcitabine, vinorelbine, and doxorubicin (GND) regimen was effective and well tolerated in patients with R/RT cell lymphoma (n=49; 28 patients with PTCL-NOS), with ORR was 65%, the median OS was 36 months, and the 5-year estimated OS rate was 32%.