Reanalysis of Ro-CHOP Shows Subtype-Specific Efficacy After Negative Primary Analysis

By Patrick Daly - Last Updated: July 22, 2024

Following a negative primary analysis for romidepsin added to frontline CHOP (Ro-CHOP) in peripheral T-cell lymphomas (PTCLs), the final five-year analysis by Camus et al found a positive efficacy benefit specifically in T-follicular helper (TFH) phenotype subgroups.

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In an accompanying article published in the Journal of Clinical Oncology, Neha Mehta-Shah, MD, MSCI, and Steven Horwitz, MD, commented on the lessons to be learned from the reanalysis of the Ro-CHOP trial.

In the final update, “the authors reclassified patients into TFH phenotype versus non-TFH and showed a near doubling of progression-free survival (PFS) for those with a TFH phenotype (19.5 vs 10.6 months; hazard ratio, 0.703; 95% CI, 0.502-0.985; P=.0395),” Dr. Mehta-Shah explained.

According to Dr. Mehta-Shah, the precedent for subtype-specific therapies in PTCL phenotypes was set by the ECHELON-2 study, where brentuximab vedotin plus CHP yielded significant improvements in PFS and overall survival (OS), with the greatest benefits seen in anaplastic large-cell lymphomas.

“In the past decade, we have learned that PTCLs derived from TFH cells … share genomic and gene expression signatures and appear to have greater sensitivity to newer classes of therapies,” Dr. Mehta-Shah said. “Concurrently, multiple studies suggest that nodal TFH lymphomas are more responsive to therapies targeting epigenetics, including the histone deacetylase inhibitor romidepsin.”

Dr. Mehta-Shah added that studies on romidepsin combinations in the relapsed or refractory setting have repeatedly shown higher rates of response and complete response and longer durations of response in TFH lymphoma subgroups.

Altogether, the analysis highlights “the importance of not just understanding the heterogeneity within these rare diseases but also embracing this knowledge in trial design,” Dr. Mehta-Shah said.

“With multiple promising agents being developed in T-cell lymphoma, it is incumbent on us to explore subtype-specific activity to enrich for those who will benefit and minimize for those who will not in the subsequent studies of these rare and difficult-to-treat diseases,” Dr. Mehta-Shah ended.

 

Reference

Mehta-Shah N, Horwitz SM. Failing forward in peripheral T-cell lymphoma. J Clin Oncol. 2024;42(14):1599-1602. doi:10.1200/JCO.23.02658

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