As reported in the Journal of Clinical Oncology by Bachy et al, the Lymphoma Study Association phase III Ro-CHOP trial showed no progression-free survival benefit with the addition of the histone deacetylase inhibitor romidepsin to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated patients with peripheral T-cell lymphoma (PTCL).
Study Details
The open-label trial included 421 adult patients from sites in nine countries in Europe, Asia, and Australia. They were randomly assigned between January 2013 and December 2017 to receive romidepsin at 12 mg/m2 on days 1 and 8 of 3-week cycles for six cycles plus CHOP in 3-week cycles for six cycles (Ro-CHOP group, n = 211) or CHOP alone (n = 210). CHOP consisted of cyclophosphamide at 750 mg/m2, doxorubicin at 50 mg/m2, and vincristine at 1.4 mg/m2 on day 1 and prednisone at 40 mg/m2 on days 1 to 5. Granulocyte colony-stimulating factor was mandatory for all patients at each cycle.
The primary endpoint was progression-free survival according to International Working Group 1999 criteria.
Progression-Free Survival
Median follow-up was 27.5 months. Median progression-free survival was 12.0 months (95% confidence interval [CI] = 9.0–25.8 months) in the Ro-CHOP group vs 10.2 months (95% CI = 7.4–13.2 months) in the CHOP group (hazard ratio [HR] = 0.81, 95% CI = 0.63–1.04, P = .096). Rates at 6 months, 1 year, and 2 years were 67.4% vs 65.9%, 49.8% vs 44.3%, and 43.2% vs 36.3%, respectively.
KEY POINTS
- The addition of romidepsin to CHOP did not improve progression-free survival.
- Grade ≥ 3 adverse events were more common in the romidepsin group.
Median overall survival was 51.8 months (95% CI = 35.7–72.6 months) in the Ro-CHOP group vs 42.9 months (95% CI = 29.9 months–not reached) in the CHOP group (HR = 0.90, 95% CI = 0.68–1.20, P = .477). Rates at 1 and 2 years were 78.2% vs 77.5% and 63.6% vs 63.4%. No significant differences were observed in objective response rates (63.0% vs 60.5%) or rates of complete response plus unconfirmed complete response (41.2% vs 37.1%).
Adverse Events
Grade ≥ 3 adverse events occurred in 93.8% of patients in the Ro-CHOP group vs 69.7% of the CHOP group, with a ≥ 10% higher rate in the RO-CHOP group for thrombocytopenia (50.0% vs 10.1%), neutropenia (49.0% vs 32.7%), anemia (46.7% vs 17.3%), leukopenia (31.9% vs 19.7%), decreased platelet count (27.6% vs 1.4%), decreased neutrophil count (26.2% vs 15.4%), decreased white blood cell count (23.3% vs 11.5%), and febrile neutropenia (21.0% vs 9.6%). Adverse events led to death in one patient in the Ro-CHOP group (due to sepsis, considered unrelated to treatment) and two patients in the CHOP group (due to colitis considered related to treatment and acute cholecystitis considered unrelated to treatment).
The investigators concluded, “The addition of romidepsin to CHOP did not improve progression-free survival, response rates, nor overall survival and increased the frequency for grade ≥ 3 treatment-emergent adverse events. Ro-CHOP does not represent a significant advance in the standard of care for patients with previously untreated PTCL.”
Emmanuel Bachy, MD, PhD, of the Hematology Department, Lyon Sud Hospital, Claude Bernard Lyon 1 University, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Celgene/Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.
