Tazemetostat and Belinostat Synergy in Relapsed/Refractory Lymphoma

At Columbia University, researchers are leveraging laboratory-driven insights to tackle the biological heterogeneity of lymphoma. Jennifer Effie Amengual, MD, is leading a national clinical trial evaluating a novel combination of 2 epigenetic drugs, tazemetostat (Tazverik) and belinostat (Beleodaq), for patients with relapsed/refractory disease. This therapeutic strategy originated in Amengual's laboratory, where preclinical studies revealed significant synergy in lymphoma subtypes—particularly those originating in the germinal center—that harbor specific mutations in epigenetic controls.

Funded by the NCI and the Cancer Therapy Evaluation Program (CTEP), the trial is currently open across the United States. Early data indicate that the dual-epigenetic approach is a well-tolerated regimen, successfully managing potential adverse effects while showing a notable enrichment of responses in T-cell lymphomas. As enrollment nears completion, the oncology community awaits formal results that could establish a more precise, biologically targeted framework for managing these complex malignancies.

Transcript:

We are fortunate at Columbia to be involved in and leading a whole host of clinical trials that really target the spectrum of lymphoma subtypes. Lymphoma is a very heterogeneous disease, and we have clinical trials that are working for many of these subtypes.

One I would like to highlight is a trial we are leading that is looking at 2 epigenetic drugs, tazemetostat and belinostat, in relapsed/refractory lymphomas. This work was developed in my laboratory, where we looked at the…preclinical application of this combination. Some lymphomas harbor mutations in epigenetic controls, which change how genes are expressed, and these tend to cluster in certain subtypes of lymphoma, especially those in the germinal center. We had this idea: can we target multiple epigenetic pathways to synergize these effects in these specific lymphomas?

Based on our work in the lab, we combined tazemetostat and belinostat and found very strong synergy in certain lymphoma subtypes, and we were able to bring this study to the clinic. This is funded through the NCI and CTEP and is open nationally. So far, we have found that it is a very well-tolerated combination, and we are seeing an enrichment of responses in T-cell lymphomas, so we are excited for the next steps. This is nearing completion of enrollment, and hopefully, we will have some signal of response that we can present soon.

Reference

Amengual JE, Tun AM, Piorczynski TB, et al. Etctn P10500: Phase 1 study of tazemetostat plus belinostat for the treatment of relapsed or refractory lymphoma. Blood. 2024;144(suppl 1):3112. doi:10.1182/blood-2024-199650