Chidamide: A New Exploration of Maintenance Therapy for DLBCL Patients with HBV Infection

Abstract Purpose: DLBCL patients with co-infection of HBV tend to have earlier onset, later staging, more rapid recurrence, and shorter survival. Currently, HBV has been shown to be involved in epigenetic regulation, so it is worth exploring whether chidamide maintenance therapy can effectively prolong the remission time and improve the long-term prognosis of DLBCL patients with HBV infection after achieving CR/PR with first-line treatment. Methods: This study prospectively investigated whether DLBCL patients with co-infection of HBV could benefit from maintenance therapy with chidamide after obtaining CR/PR with first-line therapy. This was a single-arm, single-centre, open clinical trial (NCT04661943). Chidamide maintenance therapy (20 mg biw) was given to patients with DLBCL patients who co-infection with HBV after achieving CR/PR on first-line therapy and continued for 2 years until disease progression or intolerable adverse effects occurred. To further evaluate the efficacy of chidamide maintenance therapy, we followed up the prognosis of DLBCL patients who were not infected with HBV and did not receive chidamide maintenance therapy during the same period of time in a 1:1 ratio by propensity score matching to avoid confounding bias. Results: A total of 95 DLBCL patients with HBV infection initially diagnosed at our centre from June 2017 to June 2024, 87 achieved CR/PR after 4-6 cycles of RCHOP-like regimens. And we excluded patients with other viral infections, other malignancies and specific types of lymphomas, and ultimately a total of 67 patients were enrolled in the present study.29 patients agreed to receive chidamide maintenance therapy, while 38 patients declined this recommendation. The baseline clinical data and relevant haematological findings did not show any difference between the two groups, but more patients in the chidamide maintenance group had Ann Arbor stage III-IV(p=0.006). At a median follow-up of 30 months, 15 (17.2%) patients with DLBCL co-infected with HBV experienced disease progression, relapse, or death. The survival analysis of patients in the chidamide maintenance group was better than that of the observation group, with 3-year OS rate of 83.9% vs. 59.8% (p = 0.071), even though no statistical difference was seen. Notably, the overall PFS of patients in the chidamide maintenance group was also significantly prolonged compared to the observation group, with 2-year PFS rate of 84.4% in the maintenance group versus 64.8% in the observation group (p=0.038). In addition, we also paired DLBCL patients not infected with HBV and not receiving chidamide maintenance therapy with DLBCL patients infected with HBV and not receiving maintenance therapy during the same period of time in a 1:1 ratio by PSM, and the results confirmed that DLBCL patients infected with HBV and not receiving chidamide maintenance had a significantly shorter PFS and OS when compared with DLBCL patients not infected with HBV (p= 0.023, p=0.027), which is in line with the current mainstream view. In particular, OS and PFS in the chidamide maintenance group did not differ from those in the DLBCL group without HBV infection (p=0.638, p=0.954), which means that chidamide maintenance therapy significantly improved the prognosis of DLBCL patients with HBV infection. We also evaluated the safety of chidamide, and only seven patients experienced SAEs (neutropenia, anemia, thrombocytopenia), but all were treated aggressively and effectively, and no patients were discontinued or had their dosage reduced as a result. No patients experienced non-haematological adverse events of grade III or higher. Conclusions: The administration of chidamide maintenance therapy to DLBCL patients with co-infection of HBV who achieved CR/PR after 4-6 cycles of first-line therapy significantly improved their prognosis and demonstrated good safety and tolerability, providing a new option, direction and hope for the maintenance therapy of DLBCL patients with co-infection of HBV. Key words: lymphoma; HBV; Chidamide; DLBCL; maintenance therapy