R Garcia-Sanz1, A Sureda2, F de la Cruz3, M Canales4, A P Gonzalez5, J L Pinana6, A Rodriguez7, A Gutierrez8, E Domingo-Domenech2, B Sanchez-Gonzalez9, G Rodriguez10, J Lopez11, M Moreno12, M J Rodriguez-Salazar13, S Jimenez-Cabrera14, M D Caballero15, C Martinez16. 1. Servicio de Hematología, Hospital Universitario de Salamanca; Instituto de Investigación Biomédica de Salamanca (IBSAL); Centro de Investigación del Cáncer de Salamanca, Salamanca; Servicio de Hematología, Hospital Duran i Reynals, Instituto Catalá d'Oncologia, L'Hospitalet de Llobregat, Barcelona. Electronic address: rgarcias@usal.es. 2. Servicio de Hematología, Hospital Virgen del Rocio de Sevilla, Seville. 3. Servicio de Hematología, Hospital La Paz de Madrid, Madrid. 4. Servicio de Hematología, Hospital Central de Asturias, Oviedo, Asturias. 5. Servicio de Hematología, Hospital Clínico de Valencia, Valencia. 6. Servicio de Hematología, Hospital 12 de Octubre de Madrid, Madrid. 7. Servicio de Hematología, Hospital Son Espases de Palma de Mallorca, Palma de Mallorca. 8. Servicio de Hematología, Hospital del Mar de Barcelona, Barcelona. 9. Servicio de Hematología, Hospital Gregorio Marañón, Madrid. 10. Servicio de Hematología, Hospital Ramón y Cajal, Madrid. 11. Servicio de Hematología, Hospital Germans Trias y Pujol de Badalona, Barcelona. 12. Servicio de Hematología, Hospital Universitario de Canarias, Tenerife. 13. Servicio de Farmacia, Hospital Universitario de Salamanca. 14. Pharmacy Department of Salamanca, Salamanca. 15. Servicio de Hematología, Hospital Universitario de Salamanca; Instituto de Investigación Biomédica de Salamanca (IBSAL); Centro de Investigación del Cáncer de Salamanca, Salamanca; Servicio de Hematología, Hospital Duran i Reynals, Instituto Catalá d'Oncologia, L'Hospitalet de Llobregat, Barcelona. 16. Hospital Clinic de Barcelona, Barcelona, Spain.
Abstract
BACKGROUND: 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) 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. RESULTS: 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%). CONCLUSION: BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.
BACKGROUND: 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) 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. RESULTS: 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%). CONCLUSION: BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.
Authors: Joseph M Connors; Wendy Cozen; Christian Steidl; Antonino Carbone; Richard T Hoppe; Hans-Henning Flechtner; Nancy L Bartlett Journal: Nat Rev Dis Primers Date: 2020-07-23 Impact factor: 52.329
Authors: Julia Driessen; Marie José Kersten; Lydia Visser; Anke van den Berg; Sanne H Tonino; Josée M Zijlstra; Pieternella J Lugtenburg; Franck Morschhauser; Martin Hutchings; Sandy Amorim; Thomas Gastinne; Marcel Nijland; Gerben J C Zwezerijnen; Ronald Boellaard; Henrica C W de Vet; Anne I J Arens; Roelf Valkema; Roberto D K Liu; Esther E E Drees; Daphne de Jong; Wouter J Plattel; Arjan Diepstra Journal: Leukemia Date: 2022-10-14 Impact factor: 12.883
Authors: Alex F Herrera; Joycelynne Palmer; Vikram Adhikarla; Dave Yamauchi; Erasmus K Poku; James Bading; Paul Yazaki; Savita Dandapani; Matthew Mei; Robert Chen; Thai Cao; Nicole Karras; Pamela McTague; Auayporn Nademanee; Leslie Popplewell; Firoozeh Sahebi; John E Shively; Jennifer Simpson; D Lynne Smith; Joo Song; Ricardo Spielberger; Ni-Chun Tsai; Sandra H Thomas; Stephen J Forman; David Colcher; Anna M Wu; Jeffrey Wong; Eileen Smith Journal: Blood Adv Date: 2021-12-14
Authors: Ryan C Lynch; Ryan D Cassaday; Stephen D Smith; Jonathan R Fromm; Andrew J Cowan; Edus H Warren; Mazyar S Shadman; Andrei Shustov; Brian G Till; Chaitra S Ujjani; Edward N Libby; Mary Philip; Hilary Coye; Christen N Martino; Sandra L Bhark; Karolyn Morris; Heather Rasmussen; Sanaz Behnia; Jenna Voutsinas; Ajay K Gopal Journal: Lancet Haematol Date: 2021-08 Impact factor: 30.153