Treatment with anti CD19 chimeric antigen receptor T cells after antibody-based immunotherapy in adults with acute lymphoblastic leukemia.

Abstract

PURPOSE OF THE STUDY:

The prognosis of patients with relapsed/refractory precursor B-acute lymphoblastic leukemia (ALL) is dismal. Antibody-based therapies, such as blinatumomab or inotuzumab ozogamycin (IO) have led to improved outcomes. The impact of prior immunotherapy on chimeric antigen receptor (CAR) T-Cell therapeutic efficacy and toxicity is unknown.

METHODS:

We describe a case series of ALL patients with prior exposure to blinatumomab or IO, who were treated with anti-CD19 CAR T cells with CD28 co-stimulatory domain (NCT02772198). We then review the literature on CAR-T post antibody-based therapy with either antibodies.

RESULTS:

Five adult patients with B-ALL were included. Three had active disease, and two were in morphological complete remission (CR) with minimal residual disease (MRD+). Therapy before CAR-T included blinatumomab (3/5 [60 %]) and IO (3/5 [60 %]), with one patient receiving both. One patient experienced severe cytokine release syndrome and central nervous system toxicity and subsequently died. At 28 days following treatment, two patients achieved CR with MRD negativity, and two had an MRD + CR. Two patients received allogeneic hematopoietic stem cell transplantation. At a median of 10 months (range, 5-26, three out of the four patients are still in CR, and one relapsed. The literature review identified a deficiency on data on the influence of blinatumumab and IO on outcomes post CAR-T therapy.

CONCLUSIONS:

CD19 CAR T-cell therapy after treatment with blinatumomab and/or IO in patients with relapsed/refractory B-ALL is feasible and results in promising response rates in this case series. Future trails should specifically address outcomes in this population.

• Authors: Ivetta Danylesko, Guy Chowers, Roni Shouval, Michal J Besser, Elad Jacoby, Avichai Shimoni, Arnon Nagler, Abraham Avigdor
• Journal: Current research in translational medicine (Curr Res Transl Med) Vol. 68 Issue 1 Pg. 17-22 (01 2020) ISSN: 2452-3186 [Electronic] France
• PMID: 31882377 (Publication Type: Case Reports, Journal Article, Review)
• Copyright: Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antibodies, Bispecific
• Antigens, CD19
• Antineoplastic Agents, Immunological
• CD19 molecule, human
• Protein Kinase Inhibitors
• blinatumomab
• Inotuzumab Ozogamicin

Topics

• Adult
• Antibodies, Bispecific (therapeutic use)
• Antigens, CD19 (immunology)
• Antineoplastic Agents, Immunological (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Combined Modality Therapy
• Cytokine Release Syndrome (etiology)
• Female
• Humans
• Immunotherapy (adverse effects)
• Immunotherapy, Adoptive (adverse effects, methods)
• Inotuzumab Ozogamicin (therapeutic use)
• Male
• Middle Aged
• Neoplasm, Residual
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, pathology, therapy)
• Protein Kinase Inhibitors (therapeutic use)
• Remission Induction
• Salvage Therapy