decitabine + camrelizumab

The combination of decitabine and camrelizumab is a therapeutic regimen that has shown significant efficacy in treating relapsed/refractory classical Hodgkin lymphoma (cHL), particularly in patients who have failed prior PD-1 inhibitor monotherapy. This combination leverages the epigenetic modifying properties of decitabine with the immune checkpoint inhibition of camrelizumab to enhance anti-tumor responses. ## Mechanism of Action Decitabine is a DNA methyltransferase inhibitor (DNMTi) that works by inhibiting DNA methyltransferase 1 (DNMT1), leading to DNA hypomethylation. This epigenetic modification can reactivate previously silenced tumor suppressor genes and enhance immune responses. Specifically, low-dose decitabine has been shown to increase CD8+, CD4+, and IFNγ+ T cell infiltration and broaden the peripheral T cell receptor repertoire through DNA demethylation. Camrelizumab is an anti-PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, preventing the inhibition of T cell activation and restoring anti-tumor immune responses. When combined, decitabine appears to sensitize tumors to PD-1 inhibition by camrelizumab, resulting in improved clinical outcomes compared to camrelizumab monotherapy. ## Clinical Efficacy In a randomized phase II trial involving patients with relapsed/refractory cHL who were naïve to PD-1 blockade, the combination of decitabine plus camrelizumab demonstrated: - Higher complete response (CR) rates compared to camrelizumab monotherapy (71% vs 32%) - 100% response duration at 6 months compared to 76% with monotherapy - Longer progression-free survival (PFS) compared to camrelizumab alone For patients who had previously failed PD-1 inhibitor monotherapy, decitabine plus camrelizumab showed: - Objective response rate of 52% (with 36% complete responses) in the test cohort and 68% (with 24% complete responses) in the expansion cohort - Median PFS of 20.0 and 21.6 months in the respective cohorts, significantly longer than that achieved with prior anti-PD-1 monotherapy - Durable response in an estimated 78% of patients who achieved CR at 24 months ## Dosing Regimen The typical dosing regimen used in clinical trials was: - Decitabine: 10 mg/day, days 1-5 - Camrelizumab: 200 mg, day 8 (or day 6 in some protocols) - Administered every 3 weeks ## Biomarkers After decitabine plus camrelizumab treatment, the percentage increase of circulating peripheral central memory T-cells correlated with both improved clinical response and PFS, suggesting a potential biomarker for this combination therapy. ## Safety Profile The combination therapy has shown manageable adverse events. Immune-related adverse events reported in clinical trials included myalgia, rash, diarrhea, and hypothyroidism. ## Ongoing Research Research is ongoing to further enhance the efficacy of this combination by adding other agents such as chidamide, a histone deacetylase inhibitor, for patients who are resistant to or relapse after decitabine plus camrelizumab therapy.

Brand names

AiRuiKaDacogen

Other names

anti-PD-1 monoclonal antibody-Chinese PLA General Hospital-diffuse large B-cell lymphomaanti-PD1 monoclonal antibody-Chinese PLA General Hospital-diffuse large B-cell lymphomaanti-PD 1 monoclonal antibody-Chinese PLA General Hospital-diffuse large B-cell lymphomaLow-dose decitabine plus camrelizumabDecitabine plus camrelizumabLow-dose decitabine plus anti-PD-1