Chidamide with the methotrexate, ifosfamide, etoposide, doxorubicin liposomes, and dexamethasone (MIEDD) regimen improves efficacy and safety in newly diagnosed primary CNS T-cell lymphoma

Abstract BackgroundDiffuse large B-cell lymphoma, a common subtype of primary central nervous system (CNS) lymphoma, has been increasingly studied. In contrast, advances in treating primary CNS T-cell lymphoma remain limited. Until now, a single large series exclusively describing treatment regimens and evaluating their efficacy in patients with newly diagnosed primary CNS T-cell lymphoma has not been reported. We referred to the treatment regimen for primary CNS lymphoma (high-dose methotrexate-based chemotherapies) in combination with the treatment regimen for systemic T cell lymphoma (CHOEP plus chidamide) and selected drugs that can cross the blood‒brain barrier to develop the methotrexate, ifosfamide, etoposide, doxorubicin liposomes and dexamethasone (MIEDD) regimen with or without chidamide. This study aimed to evaluate the efficacy and safety of this regimen for newly diagnosed primary CNS T-cell lymphoma.MethodsHIV-negative patients with newly diagnosed primary CNS T-cell lymphoma at Beijing Tiantan Hospital, Capital Medical University, between January 2022 and December 2024 received three-six cycles of methotrexate (3.5 g/m2) on day 1, ifosfamide (1.5 g/m2) on day 2, etoposide (100 mg/m2) on day 3, doxorubicin liposomes (25 mg/m2) on day 4, and dexamethasone (10 mg) on days 1-3, with a cycle of every 21 days. Chidamide (30 mg) was taken orally twice a week.ResultsEleven patients were included in the study, with a median age was 54 years (range, 34-74), and 3 patients (27.3%) were ≥ 60 years of age. Six patients (54.5%) were male. The median time from symptom onset to definitive diagnosis was 1.5 months (range, 0.5-5 months). The histological type of all primary CNS lymphomas was peripheral T-cell lymphoma not otherwise specified. Ten of 11 patients completed 6 cycles of induction chemotherapy; another patient received 3 cycles. Six patients (54.5%) plus 30 mg chidamide twice a week. Among them, 2 began to receive it in induction therapy, 3 received it as maintenance treatment, and 1 received it when the disease progressed after the end of 6 cycles of induction chemotherapy. After induction therapy, 8 (72.7%) patients achieved complete remission (CR), 1 (9.1%) patient achieved partial remission (PR), 1 (9.1%) patient had stable disease (SD), and 1 (9.1%) patient had progressive disease (PD). After receiving one cycle of induction chemotherapy with the MIEDD regimen, two patients were assessed as SD and PD. Beginning with the second cycle, chidamide was added to the MIEDD regimen. Prior to the fifth cycle of chemotherapy, disease evaluation achieved CR and PR. Three additional patients achieved sustained remission status with oral chidamide maintenance therapy following induction chemotherapy. At a median follow-up of 15.7 months (95% CI, 12.14–19.26), the median PFS was not reached, with an estimated PFS rate of 68.2% at 2 years. The median OS was not reached. All patients were still alive at the time this paper was written. The most common adverse events were hypocytosis and gastrointestinal symptoms. Grade 4 hematological toxicity occurred in 2 patients. No patients died of toxicity.Conclusions The preliminary results of this study show that chidamide combined with the MIEDD regimen has good efficacy and safety in the treatment of patients with newly diagnosed primary CNS T-cell lymphoma. Building on these encouraging results, we will conduct a Phase II clinical trial, in which the cerebrospinal fluid permeability of chidamide and its optimal dosage will be the key focus.