Romidepsin Plus CHOP Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Results of the Ro-CHOP Phase III Study (Conducted by LYSA)

Author(s): Emmanuel Bachy , MD, PhD1,2; Vincent Camus , MD3; Catherine Thieblemont , MD, PhD4; David Sibon , MD, PhD5; René-Olivier Casasnovas , MD6; Loïc Ysebaert , MD, PhD7; Gandhi Damaj, MD, PhD8; Stéphanie Guidez, MD9; Gian Matteo Pica, MD10; Won Seog Kim , MD, PhD11; Soon Thye Lim, MBBS12; Marc André, MD13; Alejandro Martín García-Sancho , MD, PhD14; Maria Jesus Penarrubia , MD, PhD15; Philipp B. Staber , MD, PhD16; Judith Trotman , MBChB17; Andreas Hüttmann , MD18; Vittorio Stefoni, MD, PhD19; Alessandro Re, MD20; Philippe Gaulard , MD21; Marie-Helene Delfau-Larue, MD, PhD22; Laurence de Leval, MD, PhD23; Michel Meignan , MD, PhD24; Ju Li, PhD25; Franck Morschhauser , MD, PhD26; and Richard Delarue, MD5,27;
Source: DOI: 10.1200/JCO.21.01815 Journal of Clinical Oncology 40, no. 3 (January 20, 2022) 242-251. Published online November 29, 2021. PMID: 34843406
Lucio Gordan MD

Dr. Gordan's Thoughts

Unfortunately, another negative study of a drug being accretive to CHOP regimen in T-cell NHL. Newer drugs and concepts hopefully will move the needle in this decade.

PURPOSE

Romidepsin, a histone deacetylase inhibitor, has demonstrated activity in relapsed or refractory peripheral T-cell lymphoma (PTCL) as a single agent. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used as first-line treatment of PTCL; however, it has limited efficacy. Results from a phase Ib and II study showed the feasibility of combining romidepsin with CHOP (Ro-CHOP).

METHODS

This study is a randomized phase III study of Ro-CHOP versus CHOP in adult patients with previously untreated PTCL. All patients received CHOP in 3-week cycles for six cycles. Romidepsin, 12 mg/m2, was administered intravenously over a 4-hour period on days 1 and 8 of each 3-week cycle for six cycles. The primary end point was progression-free survival (PFS) according to International Working Group 1999 criteria.

RESULTS

Between January 2013 and December 2017, 421 patients were enrolled (Ro-CHOP, n = 211; CHOP, n = 210). The median PFS for Ro-CHOP versus CHOP was 12.0 months (95% CI, 9.0 to 25.8) versus 10.2 months (95% CI, 7.4 to 13.2) with a hazard ratio of 0.81 (P = .096). In the Ro-CHOP versus CHOP arms, the median overall survival was 51.8 versus 42.9 months and the objective response rate was 63% versus 60% with complete response plus unconfirmed complete response rates of 41% versus 37% (P > .1 in all comparisons), respectively. Grade 3 or 4 treatment-emergent adverse events occurring in ≥ 30% of patients in the Ro-CHOP arm included thrombocytopenia (50% v 10% in the Ro-CHOP v CHOP arms, respectively), neutropenia (49% v 33%), anemia (47% v 17%), and leukopenia (32% v 20%).

CONCLUSION

The addition of romidepsin to CHOP did not improve PFS, 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.

Author Affiliations

1Hospices Civils de Lyon, Lyon, France 2Claude Bernard Lyon 1 University, Lyon, France 3Department of Hematology, Centre Henri Becquerel, Rouen, France 4APHP, Hôpital Saint-Louis, Service d’hémato-oncologie, DMU DHI, Université de Paris, Paris, France 5Service d’Hématologie adultes, Hopital Universitaire Necker Enfants Malades, AP-HP, Paris, France 6Department of Hematology, CHU Dijon-Bourgogne and INSERM 1231, Dijon, France 7IUCT Oncopole, Toulouse, France 8Hematology Institute, University Hospital, Normandy University, School of Medicine, Caen, France 9Service d’Hématologie, CHU de Poiters, Poiters, France 10Department of Hematology, Centre Hospitalier Métropole Savoie Chambéry, Chambéry, France 11Samsung Medical Center, Seoul, South Korea 12National Cancer Centre Singapore, Singapore 13Department of Hematology, CHU UCL Namur, Yvoir, Belgium 14Hospital Universitario de Salamanca, IBSAL, CIBERONC, Salamanca, Spain 15Hospital Clinico Universitario de Valladolid, Valladolid, Spain 16Division of Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria 17Concord Repatriation General Hospital, University of Sydney, Concord, Australia 18Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, University Hospital Essen, University of Duisburg-Essen, Essen, Germany 19Policlinico Sant’Orsola-Malpighi, Bologna, Italy 20Hematology Division, Spedali Civili di Brescia, Brescia, Italy 21Department of Pathology and Inserm U955, University Hospital Henri Mondor, Créteil, France 22Department of Immunobiology and Inserm U955, Université Hôpital Henri Mondor, Créteil, France 23Institute of Pathology, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland 24LYSA Imaging, APHP, Hôpital Henri Mondor, Université Paris Est, Créteil, France 25Bristol Myers Squibb Company, Princeton, NJ 26Univ. Lille, CHU Lille, ULR 7365 – GRITA – Groupe de Recherche sur les Formes Injectables et les Technologies Associées, Lille, France 27Celgene, a Bristol Myers Squibb Company, Boudry, Switzerland

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