Bristol Myers Squibb has decided to withdraw the approval for romidepsin, a histone deacetylase inhibitor, for the treatment of adults with peripheral T-cell lymphoma who received at least 1 prior therapy after a confirmatory phase 3 study missed its primary end point.
Bristol Myers Squibb has decided to withdraw the approval for romidepsin (Istodax), a histone deacetylase inhibitor, for the treatment of adults with peripheral T-cell lymphoma (PTCL) who received at least 1 prior therapy after a confirmatory phase 3 study missedmeet its primary end point, according to a press release by the corporation.1
The decision was made based on the results of a phase 3 (NCT01796002) clinical trial (NCT01796002) of romidepsin plus the CHOP regimen consisting of Rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, prednisone (Ro-CHOP) versus CHOP. The parallel assignment, phase 3, multicenter, open-label study enrolled approximately 421 participants. The primary end point of Ro-CHOP was the effect on progression-free survival by R0-CHOP versus CHOP alone.
“While the outcome of the confirmatory study in peripheral T-cell lymphoma is disappointing, Bristol Myers Squibb will continue to provide Istodax for patients with cutaneous T-cell lymphoma, where it remains an approved and important treatment option,” said Noah Berkowitz, MD, PhD, senior vice president of the Hematology Development at Bristol Myers Squibb in a press release. “As always, our efforts across blood cancer research and development remain centered on delivering better outcomes for patients in need.”
The study was split into 2 arms. In arm 1, patients received romidepsin plus CHOP. CHOP was administered in 3-week cycles for 6 weeks and romidepsin was administered at a dose of 12mng/m2 on day 1 and day 8 every 3 weeks. In arm 2, patients received CHOP alone.
At the 2019 data cutoff, 421 patients were included in the intention-to-treat population. Of those 421 patients, 211, received the addition of romidepsin and 210 received CHOP alone. The median age of participants was 65 years old (range, 25-81), 18% of patients had an ECOG performance status of 2-3, and 63% had Ann Arbor stage IV disease.2
At the median follow-up of 27.5%, there was not a statistically significant improvement in PFS between the RO-CHOP arm and the control arm. The median PFS for the RO-CHOP group was 12 months (95% CI, 9.0-25.8) versus 10.2 months alone (95% CI, 7.4-13.2). The median OS for the RO-CHOP group was 51.8 months (95% CI, 35.7-72.6) and 42.9 months for the CHOP arm (95% CI, 29.9-not evaluable). Additionally, the overall response rate for the RO-CHOP group was 63% with a complete response rate of 41%, and 60% for the CHOP arm with a complete response rate of 37%.
Common adverse events (AEs) in the RO-CHOP arm and the control arm respectively included anemia (67% vs 38%), nausea (55% vs 31%), thrombocytopenia (52% vs 17%), neutropenia (51% vs 37%), and vomiting (40% vs 10%). Grade 3/4 AEs included thrombocytopenia (50% vs 10%), neutropenia (49% vs 33%), anemia (47% vs 17%), and leukopenia (32% vs 20%).
In order to participate, patients must be 18 years old or older, have histologically proven PTCL, have an ECOG score of 0-2, have a negative pregnancy test, and have a life expectancy of 3 months or more. Patients with other types of lymphomas, previous radiotherapy for PTCL, central nervous system-meningeal involvement, HIV positive, known cardiac abnormalities, or a clinically significant active infection, are not eligible to participate.
Romidepsin is an epigenetic therapy injection. The agent works by the removal of acetyl groups from acetylated lysine residues in histones, which modulates gene expression. Romidepsin belongs to the histone deacetylase (HDAC) inhibitor class, which also deacetylates non-histone proteins like transcription factors. When in vitro, acetylated histones acuminate of acetylated histones and incudes cell cycles arrest and the apoptosis of some cancer cell lines. The agent was granted an accelerated approval by the FDA.