BTK Inhibitors and Chidamide-Combined Therapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma with MYC⁺

Background:

Relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) shows poor clinical outcomes, particularly in patients with MYC rearrangement or mutations. Monotherapy Bruton tyrosine kinase inhibitors (BTKi) have established modest antitumor effect in R/R DLBCL by targeting B-cell receptor signaling, with median progression-free survival (PFS) and overall survival (OS) of 1.64-2.8 months and 6.4-8.4 months, respectively. Chidamide is a selective oral histone deacetylase inhibitors (HDACi) that shows promising treatment for DLBCL and may overcome BTKi resistance. So, we evaluated the efficacy and safety of BTKis and chidamide-combined therapy in R/R DLBCL with MYC⁺ .

Methods:

This retrospective study consists of 12 R/R DLBCL who received combination therapy of chidamide and BTK inhibitors between January 2023 and July 2024. Chidamide was orally administered at a dose of 20 mg twice a week, while the BTK inhibitor was administered daily. Patient clinical characteristics were collected upon patient enrollment. Efficacy outcomes included overall response rate (ORR), PFS and OS, whereas safety outcomes included incidence of adverse events.

Results:

12 R/R DLBCL patients were enrolled. Median age was 63 years (range, 39-73), and 83.33% of the patients had non-germinal center B-cell-like (non-GCB) DLBCL, two had transformed DLBCL. The median number of previous treatment lines was 3 (range, 1-8). 10 patients (83.33%) received treatment with BTK inhibitors before. The best ORR was 66.67%, with 8 of 12 patients acquired objective disease remission after 1-2 cycles. Among them, 6 patients (50%) achieved complete response, and 2 patients (16.67%) achieved partial remission. With a median follow-up of 6.5 months, the median PFS and median OS was not yet reached. In terms of adverse events, the most common hematologic toxicities observed were neutropenia (50%, 6/12) and anemia (66.67%, 8/12). This study was registered as ChiCTR2300073233.

Conclusion:

This study revealed promising results. Chidamide combined with BTK inhibitors showed high efficacy and manageable tolerability in R/R DLBCL patients with MYC⁺. Although the majority of patients were treated with BTK inhibitors and experienced relapse and resistance, the addition of chidamide brought patients back into remission, suggesting that chidamide can enhance the efficacy of BTK inhibitors and overcome acquired resistance.

Keywords: BTK inhibitors, Chidamide, R/R DLBCL, MYC，efficacy and safety

No relevant conflicts of interest to declare.