Aspasia Stamatoullas1, Hervé Ghesquieres2, Aurore Perrot3, Philippe Quittet4, Franck Morschhauser5, Vincent Ribrag6, Veronique Edeline7, Pauline Brice8 for the LYSA group
1 Département d’Hématologie, Centre Henry Becquerel, Rouen, France, 2 Département d’Hématologie, Centre Hospitalier Lyon Sud, France, 3 Département d’Hématologie, CHU Nancy, France, 4 Département d’Hématologie, CHU Montpellier, France, 5 Département d’Hématologie, CHRU Lille, France, 6 Département of Hématologie, Institut Gustave Roussy, Paris, France, 7 Service de Médecine Nucléaire, Institut Curie, Hôpital R Huguenin, Saint-Cloud, France, 8 Département d’Hématologie, Hopital Saint Louis, Paris, France
Introduction: About 10–15% of patients with localized and 25–30% with disseminated classical HL failed to respond or relapse after primary conventional treatment. Autologous stem cell transplantation (ASCT) is a standard of care after salvage chemotherapy leading to an increased disease free survival (DFS). With this strategy 50 to 70% of patients with chemo sensitive disease become eligible for ASCT. As the disease status before ASCT appears to be the most important factor predicting outcome, second line chemotherapy has to be more efficient. Brentuximab-Vedotin (BV) has shown significant activity (SG035–0003) in patients with relapsed or refractory HL. Therefore, it seems logical to use BV in patients treated with ICE before ASCT to induce a significantly higher Complete Metabolic Response (CMR) rate evaluated by FDG-PET (Deauville score 1–3).
Methods: BV-ICE is a phase I/II trial sponsored by LYSARC with a financial support by Millenium. BV is added to ICE chemotherapy in order to increase the CMR in refractory/relapsed Hodgkin -lymphoma patients. The optimal dose of BV with ICE (3 cycles) was established and validated by the independent data monitoring committee (IDMC), in the first part of the study and applied in the second part (phase II) where efficacy and toxicity were assessed after 2 cycles of treatment.
Primary endpoint of Recommended Phase II Dose (RP2D) and CMR after 2 cycles of treatment (early futility analysis by Lugano classification 2014) are reported here.
Results: Ten patients were included in phase I. Four and six patients received 1.2 mg/kg and 1.8 mg/kg of BV respectively. Thirteen patients were included in the first part of phase II with the recommended dose of BV: 1.8 mg/kg. Baseline characteristics of the 23 patients were median age: 28 years (range: 18–55), Sex ratio (M/F): 17/6, and status of the disease: 11 refractory patients and 12 relapsed patients.
Most of patients (78%, n = 18) had CMR at the end of cycle 2 followed by PMR (13%, n = 3). Two patients (9%) had no metabolic response or progressive metabolic disease. Grade 3–4 adverse events were encountered in 18 patients (78%) mainly due to hematologic toxicity (52%) followed by infection (17%) and gastro-intestinal disorders (9%) No death was observed.
Conclusion: This study recommends a dose of 1.8 mg/kg of BV in R/R HL patients who are treated by ICE chemotherapy and shows encouraging results of efficacy with 78% of CMR after 2 cycles of treatment and acceptable toxicity.