Garcia-Sanz, RSureda, Ade la Cruz, FCanales, MGonzalez, A PPinana, J LRodriguez, AGutierrez, ADomingo-Domenech, ESanchez-Gonzalez, BRodriguez, GLopez, JMoreno, MRodriguez-Salazar, M JJimenez-Cabrera, SCaballero, M DMartinez, C2023-01-252023-01-252019http://hdl.handle.net/10668/13432In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before autologous stem-cell transplantation (ASCT). This was a multicenter, open-label, phase I-II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day ‒1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT. A total of 66 patients were recruited (median age 36 years; range 18-66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including 3 deaths. Grade 3-4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade ≥3-4 extrahematological adverse events (≥5%) were non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). Sixty-four patients underwent stem-cell mobilization; all collected >2×10e6/kg CD34+ cells (median 5.75; range 2.12-33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%). BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Hodgkin lymphomabrentuximab vedotinpolychemotherapyrefractorytransplantAdministration, IntravenousAdolescentAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBrentuximab VedotinChemotherapy-Induced Febrile NeutropeniaCisplatinCytarabineDose-Response Relationship, DrugDrug Administration ScheduleEtoposideFemaleFollow-Up StudiesHematopoietic Stem Cell TransplantationHodgkin DiseaseHumansKaplan-Meier EstimateMaleMiddle AgedNeoadjuvant TherapyNeoplasm Recurrence, LocalPrednisoneProgression-Free SurvivalSalvage TherapyTransplantation, AutologousYoung Adultresearch article30657848open access10.1093/annonc/mdz0091569-8041http://www.annalsofoncology.org/article/S0923753419311081/pdf