CAR-based Cellular Therapy: clinical ePoster


  • V. Ortiz-Maldonado
  • A. Alonso-Saladrigues
  • M. Caballero-Baños
  • M. Castellà
  • A. Boronat
  • E. García-Rey
  • T. Baumann
  • M. Díaz-Beyá
  • M. Torrebadell
  • A. Faura
  • A. Català
  • F. Ramos
  • A. Palomino
  • M. Gómez-Hernando
  • C. Jiménez-Vicente
  • J. Cid
  • M. Lozano
  • C. Llanos
  • A. Téllez
  • S. Fernández
  • P. Castro
  • I. Jordán
  • J. Esteve
  • J. Canals
  • E. Trias
  • J. Yagüe
  • M. Suárez-Lledó
  • M. Rovira
  • A. Urbano
  • M. Juan
  • S. Rives
  • J. Delgado


Sinusoidal obstruction syndrome (SOS) is a life-threatening adverse event occurring mostly in the context of allogeneic hematopoietic stem cell transplant (alloHCT), with a mean incidence of approximately 14% (2-31%, depending on conditioning regimen and individual patient risk factors). Novel immunotherapy agents like inotuzumab-ozogamicin (IO) can also increase the risk of SOS in this setting. In the pivotal trial, the risk of SOS was 8.6% for patients who received standard of care therapy plus alloHCT and 24.6% for those who received IO plus alloHCT (Kantarjian HM, 2019). However, there is little data on the incidence of SOS after other novel agents like CAR-T cells.

The first academic pilot clinical trial ( NCT03144583) using our fully academic (A3B1:CD8:4-1BB:CD3Z) CAR19 (ARI-0001 cells) finished recruitment in June/2019. Eligibility criteria included CD19+ R/R B-ALL (adult and pediatric), NHL and CLL who had failed standard available therapy. Lymphodepletion was with fludarabine (90 mg/m2) and cyclophosphamide (900 mg/m2), and the cell dose was 0.4-5 x106 ARI-0001 cells/kg, first as a single infusion (first 15 patients, cohort 1), and then in 2-3 fractions (last 23 patients, cohort 2). Here we report a descriptive analysis on the incidence of SOS in B-ALL patients included in this trial.

We treated 38 R/R B-ALL patients with ARI-0001 cells. Median age was 24.5 years (3-68). All but 5 patients had relapsed after alloHCT (33/38 = 86.8%), and among patients with history of IO treatment (15/38 = 39.4%) only one had not previously undergone an alloHCT. We observed a total of 3 (7.9%) cases of SOS (see table 1) after ARI-0001 treatment, all occurring at cohort 2. The first 2 cases where 2 adult patients of 54 and 68 years diagnosed using the modified Seattle criteria in the context of weight gain, ascites, severe thrombocytopenia, increase in transhepatic gradient, and finally, confirmed by transjugular liver biopsy at day +31 and +49 after ARI-0001 cell infusion. Both patients had previous history of alloHCT and IO treatment with an inconclusive history of liver toxicity after IO treatment. They improved clinically from their SOS with support treatment and were eventually discharged from hospital. The third SOS case occurred in a post alloHCT young female patient (19 years) that after receiving ARI-0001 cell therapy was treated in another hospital with IO (day +161) and shortly after was diagnosed and treated as a SOS at day +171. This patient improved clinically after defibrotide treatment and was eventually discharged from hospital.

[Table 1]


The incidence of SOS in patients with R/R B-ALL treated with ARI-0001 cells was 7.9%. However, it was 20% among those patients with both alloHCT and IO treatment. No SOS occurred in patients without prior alloHCT plus IO treatment. These results led us to incorporate liver imaging studies to our screening tests in patients with prior alloHCT/IO history who are referred for ARI-0001 cell therapy.

Clinical Trial Registry:
Phase I, CART19-BE-01 clinical trial (EudraCT: 2016-002972-29, NCT03144583) for relapsed/refractory CD19+ leukemia and lymphoma at the Hospital Clínic de Barcelona and Hospital Sant Joan de Déu, Barcelona (Spain).

Source of funding: Proyecto ARI; Fundació Gloria Soler; ISCIII; CatSalut; FEHH; Generalitat de Catalunya