High Response RATE and NO Treatment Related Mortality After Brentuximab Vedotin Salvage Therapy Followed by Reduced Intensity Conditioning Regimen Allogeneic STEM CELL Transplantation (RIC-ALLO) in Patients with CD 30+ Lymphomas
Authors: Furst Sabine , Bouabdallah Reda , Coso Diane , Crocchiolo Roberto , El-Cheikh Jean , Faucher Catherine , Granata Angela , Oudin Claire , Venton Geoffroy , Stoppa Anne Marie , Lemarie Claude , Chabannon Christian , Blaise Didier 
Published: October 2019

Abstract
Abstract 4526

Introduction:
Patients with relapsed or refractory Hodgkin (HL) and systemic anaplastic large cell lymphomas (sALCL) have poor outcome. RIC-allo might represent an attractive treatment option with curative potential for some patients (pt), but relapse or progression remain the major cause of failure. Pre-transplant disease control is the most important prognostic factor for long term survival and therefore salvage strategies to improve response rates are crucial. Recently, Brentuximab vedotin (BV), a antibody-drug conjugate, has been demonstrated to induce high tumor responses with moderate adverse effects in those high risk pt.

Aim and methods:
To analyse retrospectively the outcome of pt with CD 30+ HL and sALCL who underwent RIC-allo after BV salvage therapy in our center. BV was administered intravenously (iv) at 1.8mg/kg over 30 minutes every three weeks in the outpatient department.

Results:
Nine adult pt with histological proved CD30+ lymphomas underwent RIC-allo between February 2010 and Mai 2012. The median age was 36 years (range, 21–59) with 56% males. Diagnosis were HL in 6 pt (67%) and sALCL ALK+ in 3 pt (33%). All pt had highly advanced disease and received a median of 3 prior chemotherapy lines (range, 2–5) including autologous transplantation (78%) before BV treatment: Two pt had primary refractory disease (22%), 2 pt were refractory to front line chemotherapy (22%) and 5 pt were refractory to the most recent treatment (56%).
RIC-allo consisted in Fludarabine 150mg/m2 iv (Flu), Busulfan 260mg/m2 iv and ATG (Thymoglobuline) 5mg/kg for matched sibling (2 pt) and 10/10 matched unrelated donors (2 pt); Cyclophosphamide 29mg/kg (Cy), Flu 150 mg/m2 and low dose total body irradiation (TBI) 200cGy for related haploidentical donors (4 pt) and Cy 50mg/kg, Flu 200mg/m2 and TBI 200cGy for one cord blood recipient. Graft versus host disease (GvHD) prophylaxis was either Ciclosporine (CSA) alone or CSA and Mycophenolatemofetil (MMF), while pt with haploidentical donors had posttransplant high dose Cy (100mg/kg). Pt received a median of 7 BV infusions (range, 4–9) before RIC-allo. One pt had autologous transplantation followed by RIC-allo in a tandem procedure. The median time from the first BV infusion to RIC-allo was 189 days (range, 75–391) ? All pt achieved objective best responses after 2 to 3 cycles of BV. At time of RIC-allo, 6 pt were in CR (67%) and 3 pt in PR (33%). All pt engrafted. Three pt developped grade 2 acute GvHD and 2 pt extensive chronic GvHD. After a median follow-up of 275 days (range, 90–872), 7 pt are in CR (78%). Two pt with sALCL experienced relapse at a median time of 87 days after RIC-allo (54, 120), whereas 1 pt died at day 274 of disease progression. No treatment related mortality was observed.

Conclusion:
Although the study population is small and the follow-up is short, BV as salvage treatment for advanced CD30+ lymphomas may allow to reduce tumour burden to proceed to RIC-allo with sufficient disease control to benefit from a graft versus lymphoma effect. No negative impact on engraftment, GvHD or survival occurred.
Randomized prospective trials are necessary to further investigate the role of BV in pre- and post-transplant treatment strategies.

Disclosures:
No relevant conflicts of interest to declare.