Brentuximab Vedotin and ESHAP is Highly Effective as Second-Line Therapy for Hodgkin Lymphoma Patients (Long-Term Results of a Trial by the Spanish GELTAMO Group)
Mené sur 66 patients atteints d'un lymphome hodgkinien (âge médian : 36 ans), cet essai de phase I/II évalue la dose maximale tolérée, l'efficacité, du point de vue du taux de réponse globale et du taux de réponse complète avant une greffe autologue de cellules souches, et la toxicité d'un traitement de deuxième ligne combinant brentuximab védotin et chimiothérapie de type ESHAP (durée moyenne de suivi : 27 mois)
Purpose : In 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). Patients and Methods : 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) IV 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 endpoints for evaluation were maximum tolerable dose and overall and complete response before ASCT. Results : 66 patients were recruited (median age, 36yr; 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 three 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). 64 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 84-98%), including 70% complete responses (CR, 95% CI 59-81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82%, CI 73-91%) and partial responses in six (10%, CI 5-15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI, 68-80%), progression-free survival 71% (95% CI, 65-77%), and overall survival 91% (CI, 84-98%). Conclusion : BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.
Annals of Oncology 2019