René-Olivier Casasnovas1, Reda Bouabdallah2,3, Pauline Brice4, Julien Lazarovici5, Hervé Ghesquieres6, Aspasia Stamatoullas7, Jehan Dupuis8, Anne-Claire Gac9, Thomas Gastinne10, Bertrand Joly11, Krimo Bouabdallah12, Emmanuelle Nicolas-Virelizier13, Pierre Feugier14, Franck Morschhauser15, David Sibon16, Christophe Bonnet17, Alina Berriolo-Riedinger18, Véronique Edeline19, Marie Parrens20, Diane Damotte21, Diane Coso2, Marc André22,23, Michel Meignan24, Cédric Rossi1. 1. Department of Hematology, University Hospital F. Mitterrand and Inserm UMR 1231, Dijon, France. 2. Department of Hematology, Institut P. Calmette, Marseille, France. 3. Department of Hematology, Hopital privé de Provence, Aix en Provence, France. 4. Department of Hematology, APHP, Hopital Saint Louis, Paris, France. 5. Department of Hematology, Institut G. Roussy, Villejuif, France. 6. Department of Hematology, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, et Université Claude Bernard Lyon-1, Pierre Bénite, France. 7. Department of Hematology, Centre H. Becquerel, Rouen, France. 8. Lymphoid Malignancies Unit, Henri Mondor University Hospital, Créteil, France. 9. Department of Hematology, Institut d'hématologie de basse normandie, Caen, France. 10. Department of Hematology, University Hospital of Nantes, Nantes, France. 11. Department of Hematology, Hospital Sud Francilien, Corbeille-Essonnes, France. 12. Department of Hematology, University Hospital of Bordeaux, Bordeaux, France. 13. Department of Hematology, Centre L. Bérard, Lyon, France. 14. Department of Hematology, University Hospital of Nancy, Vandoeuvre les Nancy, France. 15. Department of Hematology, CHU Lille, Unité GRITA, Université de Lille 2, Lille, France. 16. Department of Hematology, Hopital Necker, Paris, France. 17. Department of Hematology, University Hospital Liege, Liege, Belgium. 18. Department of Nuclear Medicine, Centre G.F. Leclerc, Dijon, France. 19. Department of Nuclear Medicine, Hopital R. Huguenin, Institut Curie, St-Cloud, France. 20. Department of Pathology, University Hospital of Bordeaux and Inserm UMR 1053, Bordeaux, France. 21. Department of Pathology, Université de Paris et GH Paris Centre APHP, Paris, France. 22. Department of Hematology, CHU UCL Namur, Université catholique de Louvain, Yvoir, Belgium. 23. Pole Mont, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium. 24. Department of Nuclear Medicine, University Hospital H. Mondor, Creteil, France.
Abstract
PURPOSE: The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results. METHODS: Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2- and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment. RESULTS: In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% v 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; P = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; P = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2-/PET4-, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4- and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; P < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4- patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; P = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; P = .038) had a significant lower OS than PET2-/PET4- patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively. CONCLUSION: The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.
PURPOSE: The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results. METHODS: Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2- and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment. RESULTS: In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% v 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; P = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; P = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2-/PET4-, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4- and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; P < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4- patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; P = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; P = .038) had a significant lower OS than PET2-/PET4- patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively. CONCLUSION: The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.