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, PhD^1,2; 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, MD^5,27;

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

Dr. Lucio 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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