BMS Withdraws Romidepsin Indication for Peripheral T-Cell Lymphoma Following Phase III Confirmatory Trial Failure

Bristol-Myers Squibb (BMS) recently announced that it is withdrawing the indication for romidepsin for the treatment of peripheral T-cell lymphoma (PTCL) from the U.S. market. This decision is based on a confirmatory Phase III clinical trial that failed to meet its primary endpoint.

In 2011, romidepsin received accelerated approval from the FDA as monotherapy for the treatment of peripheral T-cell lymphoma (PTCL) in adult patients who have received at least one prior systemic therapy. This accelerated approval was based on the results of two clinical trials evaluating the effect of romidepsin on the surrogate endpoint of overall response rate.

Subsequently, Bristol-Myers Squibb conducted a confirmatory Phase III clinical trial to evaluate the efficacy of romidepsin + CHOP (Ro-CHOP) versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as first-line therapy for patients with PTCL, but the trial failed to meet its primary efficacy endpoint of progression-free survival. In light of these results, Bristol-Myers Squibb decided to withdraw the indication. Peripheral T-cell lymphoma (PTCL) refers to a highly heterogeneous group of aggressive non-Hodgkin lymphomas (NHL) originating from mature thymic T cells or NK/T cells, accounting for 10% of all NHL cases in Europe and the United States, whereas this proportion reaches as high as 24% in Asian populations.

It is estimated that approximately 13,100 to 15,700 new cases of peripheral T-cell lymphoma (PTCL) are diagnosed annually in China. Romidepsin is a selective histone deacetylase (HDAC) inhibitor and belongs to a class of epigenetic therapies. By inhibiting HDAC activity, romidepsin modulates histone acetylation status, promotes the transcription and expression of anti-tumor transcription factors, and regulates associated signaling pathways, thereby exerting anti-tumor biological effects. It promotes cellular differentiation, induces cell cycle arrest, triggers apoptosis, and upregulates the expression of tumor suppressor genes such as p21^CIP/WAF1, ultimately exerting anti-tumor effects.

In 2009, romidepsin was approved by the U.S. FDA for the treatment of patients with cutaneous T-cell lymphoma (CTCL) who have received at least one prior systemic therapy, and in 2011, it received FDA approval for the treatment of PTCL. Noah Berkowitz, M.D., Senior Vice President of Hematology Research and Development at Bristol-Myers Squibb, stated: “Although the results of the confirmatory trial in peripheral T-cell lymphoma are disappointing, BMS will continue to provide romidepsin to patients with CTCL. For CTCL, it remains an approved and important treatment option. As always, our efforts in blood cancer research and development remain committed to delivering better outcomes for patients in need.”