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. 2022 Jan 31:12:828471.
doi: 10.3389/fonc.2022.828471. eCollection 2022.

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

Valentín Ortiz-Maldonado  1   2 , Gerard Frigola  3 , Marta Español-Rego  4 , Olga Balagué  2   3 , Nuria Martínez-Cibrián  1 , Laura Magnano  1   2 , Eva Giné  1   2   5 , Mariona Pascal  4 , Juan G Correa  1 , Alexandra Martínez-Roca  1 , Joan Cid  2   6 , Miquel Lozano  2   6   7 , Neus Villamor  2   5   8 , Daniel Benítez-Ribas  2   4 , Jordi Esteve  1   2   7   9 , Armando López-Guillermo  1   2   5   7 , Elías Campo  2   3   5   7   8 , Álvaro Urbano-Ispizua  1   2   7   9 , Manel Juan  2   4   7 , Julio Delgado  1   2   5   7
Affiliations

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

Valentín Ortiz-Maldonado et al. Front Oncol. .

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.

Keywords: CART; CD19; CLL; DLBCL; Richter disease.

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Conflict of interest statement

VO-M: Consultant or advisory role (Kite Gilead, Celgene, Novartis), travel grants (Kite Gilead, Celgene, Novartis, Roche, Takeda, Janssen), honoraria (Kite Gilead). EG: Consultant or advisory role (Kite Gilead, Janssen, Genmab), research funding (Kite Gilead, Janssen, Roche). AM-R: Consultant or advisory role (Bristol Myers Squibb, Abbvie), travel grants (Kite Gilead, Roche, Takeda, Janssen, Abbvie), honoraria (Abbvie). ML: Honoraria (Grifols, Fresenius Kabi), research funding (Terumo BCT, Maco-Pharma). JE: Consultant or advisory role (Abbvie, Novartis, Celgene, Astellas, Jazz, Daiichi Dankyo, Roche, Amgen, Pfizer), travel grants (Celgene, Roche, Astellas, Daiichi Dankyo), research funding (Novartis, Celgene). AL-G: Consultant or advisory role (Roche, Kite Gilead, Celgene/Bristol-Myers, Incyte), honoraria (Roche, Novartis, Takeda, Bayer, Sandoz, Kern), research grants (Roche, Kite Gilead, Celgene/Bristol-Myers, Novartis, Incyte, Janssen, Pfizer, Takeda). ÁU-I: Consultant or advisory role (Kite Gilead, Celgene, Miltenyi), travel grants (Kite Gilead, Celgene). MJ: Consultant or advisory role (Kite Gilead, Grifols), honoraria (Kite Gilead, Grifols). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Duration of B-cell aplasia (A) and CD4+ cell counts below 200/µL (B) in patients who received ARI-0001 cell therapy. Overall survival from cell infusion (C) or signature of the informed consent (D). Panels (A–C) only include patients who received therapy, while panel (D) include all patients included in the program (intention-to-treat).
Figure 2
Figure 2
ARI-0001 expansion over time, calculated by quantitative PCR, in patients with CLL/RT. Lines represent median values.
Figure 3
Figure 3
Lymph node morphology and phenotype observed in patients 5 and 6 at both study inclusion and relapse after treatment with ibrutinib-primed ARI-0001 cells. In both cases, CD19 expression was lost upon relapse.
See this image and copyright information in PMC

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