Results of ARI-0001 CART19 Cells in Patients With Chronic Lymphocytic Leukemia and Richter's Transformation.

Valentín Ortiz‐Maldonado ,Manel Juan,Gerard Frigola,Joan Cid,Neus Villamor,Mariona Pascal,Marta Español-Rego,Olga Balagué,Julio Delgado,Jordi Esteve,Laura Magnano,Miquel Lozano,Eva Giné,Alexandra Martínez‐Roca ,Juan Gonzalo Correa ,Elı́as Campo ,Armando López‐Guillermo ,Núria Martínez‐Cibrián ,Daniel Benítez‐Ribas ,Álvaro Urbano-Ispízua

doi:10.3389/fonc.2022.828471

Abstract

CART19 cells are emerging as an alternative therapy for patients with chronic lymphocytic leukemia (CLL). Here we report the outcome of nine consecutive patients with CLL treated with ARI-0001 CART19 cells, six of them with Richter’s transformation (RT). One patient with RT never received therapy. The cytokine release syndrome rate was 87.5% (12.5% grade ≥3). Neurotoxicity was not observed in any patient. All patients experienced absolute B-cell aplasia, and seven (87.5%) responded to therapy. With a median follow-up of 5.6 months, two patients with RT experienced a CD19-negative relapse. In conclusion, ARI-0001 cell therapy was feasible, safe, and effective in patients with high-risk CLL or RT.

Highlights

Patients with chronic lymphocytic leukemia (CLL) who do not respond to targeted therapies have an unfavourable prognosis, if tumor cells harbour high-risk genomic aberrations (e.g. TP53 aberrations or complex karyotype) or the disease has transformed into diffuse large B-cell lymphoma (DLBCL), known as Richter’s transformation (RT) [1]
Two patients presented here were recruited into the CART19-BE-01 study [7], and the remaining patients were included in a compassionate use program (CUP) with the same inclusion criteria: (i) CD19-positive B-cell malignancy; (ii) age from 2 to 80 years; (iii) ECOG performance status 0-2; (iv) estimated life expectancy from 3 months to 2 years; and (v) adequate venous access [7]
We report the outcome of nine consecutive patients with CLL treated with ARI-0001 cells, six of them with concomitant RT (Table 1)

Summary

Introduction

Patients with chronic lymphocytic leukemia (CLL) who do not respond to targeted therapies have an unfavourable prognosis, if tumor cells harbour high-risk genomic aberrations (e.g. TP53 aberrations or complex karyotype) or the disease has transformed into diffuse large B-cell lymphoma (DLBCL), known as Richter’s transformation (RT) [1]. Current guidelines recommend allogeneic hematopoietic cell transplantation (alloHCT) for patients with high-risk CLL or RT [1,2,3]. Chimeric antigen receptor T-cells targeting CD19 (CART19) are emerging as alternative options for these patients, even though there are currently no approved products for them. At Hospital Clinic of Barcelona, we have developed our own CART19 product (A3B1:CD8:41BB : CD3z or ARI-0001), which has been recently approved by the Spanish Medicines Agency (AEMPS) for the treatment of patients with relapsed/refractory acute lymphoblastic leukemia (ALL) older than 25 years of age [4]. The aim of this paper is to report the outcome of all consecutive patients with CLL treated with ARI-0001 cells, either within the CART19-BE-01 trial or a subsequent compassionate use program (CUP)

Objectives

Methods

Conclusion