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Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure
- Source :
- Blood. 135(19)
- Publication Year :
- 2019
-
Abstract
- We previously reported durable responses in relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) patients treated with CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T-cell immunotherapy after ibrutinib failure. Because preclinical studies showed that ibrutinib could improve CAR T cell-antitumor efficacy and reduce cytokine release syndrome (CRS), we conducted a pilot study to evaluate the safety and feasibility of administering ibrutinib concurrently with CD19 CAR T-cell immunotherapy. Nineteen CLL patients were included. The median number of prior therapies was 5, and 17 patients (89%) had high-risk cytogenetics (17p deletion and/or complex karyotype). Ibrutinib was scheduled to begin ≥2 weeks before leukapheresis and continue for ≥3 months after CAR T-cell infusion. CD19 CAR T-cell therapy with concurrent ibrutinib was well tolerated; 13 patients (68%) received ibrutinib as planned without dose reduction. The 4-week overall response rate using 2018 International Workshop on CLL (iwCLL) criteria was 83%, and 61% achieved a minimal residual disease (MRD)-negative marrow response by IGH sequencing. In this subset, the 1-year overall survival and progression-free survival (PFS) probabilities were 86% and 59%, respectively. Compared with CLL patients treated with CAR T cells without ibrutinib, CAR T cells with concurrent ibrutinib were associated with lower CRS severity and lower serum concentrations of CRS-associated cytokines, despite equivalent in vivo CAR T-cell expansion. The 1-year PFS probabilities in all evaluable patients were 38% and 50% after CD19 CAR T-cell therapy, with and without concurrent ibrutinib, respectively (P = .91). CD19 CAR T cells with concurrent ibrutinib for R/R CLL were well tolerated, with low CRS severity, and led to high rates of MRD-negative response by IGH sequencing.
- Subjects :
- Oncology
Adult
Male
medicine.medical_specialty
medicine.medical_treatment
Chronic lymphocytic leukemia
Immunology
Antigens, CD19
Receptors, Antigen, T-Cell
Salvage therapy
Biochemistry
Immunotherapy, Adoptive
chemistry.chemical_compound
Piperidines
hemic and lymphatic diseases
Internal medicine
medicine
Humans
Aged
Retrospective Studies
Salvage Therapy
business.industry
Adenine
Cell Biology
Hematology
Immunotherapy
Leukapheresis
Middle Aged
medicine.disease
Prognosis
Minimal residual disease
Combined Modality Therapy
Leukemia, Lymphocytic, Chronic, B-Cell
Cytokine release syndrome
Leukemia
chemistry
Drug Resistance, Neoplasm
Ibrutinib
Feasibility Studies
Female
business
Follow-Up Studies
Subjects
Details
- ISSN :
- 15280020
- Volume :
- 135
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....98b449c71ca830002004e4c2f1008159