ASH 2024 | Long-term follow-up of a Phase II study combining azacitidine with CHOP in previously untreated PTCL

At this year’s ASH, we provided a long-term follow-up of our Phase II study, which combines the epigenetic agent azacitidine, which is a hypomethylation agent, in combination with the standard CHOP induction chemotherapy for patients with previously untreated peripheral T-cell lymphoma. Our early data was published last year at the Blood Journal. So in that initial report, we had 21 patients enrolled, and 17 of them had the follicular helper T-cell subtype, which has susceptibility and therefore we think is more sensitive to epigenetic hypomethylation. So indeed, we observed a 75% complete remission rate after induction. And we also profiled genetic mutations and tried to understand if there are any biomarkers that we can use to predict treatment response or durability or resistance. So at this year’s ASH, we are reporting a five-year follow-up. So it turns out that the median overall survival for this cohort was about 60 months and the median progression-free survival is about 40 months. Interestingly, and I think it’s important to note that with the survival curve, PFS and OS, we saw ongoing events which suggest that there does not appear to be a therapeutic plateau with induction therapy of azacitidine plus CHOP. So therefore, an additional induction strategy and also consolidation approach might be needed in order to prolong the survival outcome. And we looked at what happened to those patients who had disease progression. So it looks like most of them received novel agents as second-line or third-line treatment. Some examples include HDAC inhibitors such as romidepsin, PI3 kinase inhibitor duvelisib, and anti-CD30 antibody drug conjugate, such as BV. So two of the patients who relapsed subsequently went on to allogeneic stem cell transplant for consolidation. So therefore, the overall survival status appears to be prolonged with our induction regimen but also with the epigenetic sensitization for induction – that’s one of the lessons we learned. Secondly, I think there continue to be unmet needs and we hope that we’ll continue to develop novel combinations or adding additional treatment strategies to frontline chemotherapy. The third lesson that we’ve learned is that we have more options now for patients who progressed or relapsed. Instead of going back to more chemotherapy, more and more often we actually resort to new agents, which have a biological mechanism of action and are pretty well tolerated and do provide response and durability after salvage therapy.

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