Emmanuel Bachy1,2, Vincent Camus3, Catherine Thieblemont4, David Sibon5, René-Olivier Casasnovas6, Loïc Ysebaert7, Gandhi Damaj8, Stéphanie Guidez9, Gian Matteo Pica10, Won Seog Kim11, Soon Thye Lim12, Marc André13, Alejandro Martín García-Sancho14, Maria Jesus Penarrubia15, Philipp B Staber16, Judith Trotman17, Andreas Hüttmann18, Vittorio Stefoni19, Alessandro Re20, Philippe Gaulard21, Marie-Helene Delfau-Larue22, Laurence de Leval23, Michel Meignan24, Ju Li25, Franck Morschhauser26, Richard Delarue5,27. 1. Hospices Civils de Lyon, Lyon, France. 2. Claude Bernard Lyon 1 University, Lyon, France. 3. Department of Hematology, Centre Henri Becquerel, Rouen, France. 4. APHP, Hôpital Saint-Louis, Service d'hémato-oncologie, DMU DHI, Université de Paris, Paris, France. 5. Service d'Hématologie adultes, Hopital Universitaire Necker Enfants Malades, AP-HP, Paris, France. 6. Department of Hematology, CHU Dijon-Bourgogne and INSERM 1231, Dijon, France. 7. IUCT Oncopole, Toulouse, France. 8. Hematology Institute, University Hospital, Normandy University, School of Medicine, Caen, France. 9. Service d'Hématologie, CHU de Poiters, Poiters, France. 10. Department of Hematology, Centre Hospitalier Métropole Savoie Chambéry, Chambéry, France. 11. Samsung Medical Center, Seoul, South Korea. 12. National Cancer Centre Singapore, Singapore. 13. Department of Hematology, CHU UCL Namur, Yvoir, Belgium. 14. Hospital Universitario de Salamanca, IBSAL, CIBERONC, Salamanca, Spain. 15. Hospital Clinico Universitario de Valladolid, Valladolid, Spain. 16. Division of Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria. 17. Concord Repatriation General Hospital, University of Sydney, Concord, Australia. 18. Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. 19. Policlinico Sant'Orsola-Malpighi, Bologna, Italy. 20. Hematology Division, Spedali Civili di Brescia, Brescia, Italy. 21. Department of Pathology and Inserm U955, University Hospital Henri Mondor, Créteil, France. 22. Department of Immunobiology and Inserm U955, Université Hôpital Henri Mondor, Créteil, France. 23. Institute of Pathology, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland. 24. LYSA Imaging, APHP, Hôpital Henri Mondor, Université Paris Est, Créteil, France. 25. Bristol Myers Squibb Company, Princeton, NJ. 26. Univ. Lille, CHU Lille, ULR 7365 - GRITA - Groupe de Recherche sur les Formes Injectables et les Technologies Associées, Lille, France. 27. Celgene, a Bristol Myers Squibb Company, Boudry, Switzerland.
Abstract
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.
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.
Authors: Martin Dreyling; Marc André; Nicola Gökbuget; Hervé Tilly; Mats Jerkeman; John Gribben; Andrés Ferreri; Pierre Morel; Stephan Stilgenbauer; Christopher Fox; José Maria Ribera; Sonja Zweegman; Igor Aurer; Csaba Bödör; Birgit Burkhardt; Christian Buske; Maria Dollores Caballero; Elias Campo; Bjoern Chapuy; Andrew Davies; Laurence de Leval; Jeanette Doorduijn; Massimo Federico; Philippe Gaulard; Francesca Gay; Paolo Ghia; Kirsten Grønbæk; Hartmut Goldschmidt; Marie-Jose Kersten; Barbara Kiesewetter; Judith Landman-Parker; Steven Le Gouill; Georg Lenz; Sirpa Leppä; Armando Lopez-Guillermo; Elizabeth Macintyre; Maria Victoria Mateos Mantega; Philippe Moreau; Carol Moreno; Bertrand Nadel; Jessica Okosun; Roger Owen; Sarka Pospisilova; Christiane Pott; Tadeusz Robak; Michelle Spina; Kostas Stamatopoulos; Jan Stary; Karin Tarte; Allessandra Tedeschi; Catherine Thieblemont; Ralf Ulrich Trappe; Lorenz H Trümper; Gilles Salles Journal: Hemasphere Date: 2022-05-19
Authors: S Horwitz; O A O'Connor; B Pro; L Trümper; S Iyer; R Advani; N L Bartlett; J H Christensen; F Morschhauser; E Domingo-Domenech; G Rossi; W S Kim; T Feldman; T Menne; D Belada; Á Illés; K Tobinai; K Tsukasaki; S-P Yeh; A Shustov; A Hüttmann; K J Savage; S Yuen; P L Zinzani; H Miao; V Bunn; K Fenton; M Fanale; M Puhlmann; T Illidge Journal: Ann Oncol Date: 2021-12-16 Impact factor: 51.769
Authors: Mostafa F Mohammed Saleh; Ahmed Kotb; Ghada E M Abdallah; Ibrahim N Muhsen; Riad El Fakih; Mahmoud Aljurf Journal: Curr Oncol Date: 2021-12-20 Impact factor: 3.677