{"doi":"10.1182/blood.2020006770","title":"Factors associated with outcomes after a second CD19-targeted CAR T-cell infusion for refractory B-cell malignancies","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy has shown significant efficacy for relapsed or refractory (R/R) B-cell malignancies. Yet, CD19 CAR T cells fail to induce durable responses in most patients. Second infusions of CD19 CAR T cells (CART2) have been considered as a possible approach to improve outcomes. We analyzed data from 44 patients with R/R B-cell malignancies (acute lymphoblastic leukemia [ALL], n = 14; chronic lymphocytic leukemia [CLL], n = 9; non-Hodgkin lymphoma [NHL], n = 21) who received CART2 on a phase 1/2 trial (NCT01865617) at our institution. Despite a CART2 dose increase in 82% of patients, we observed a low incidence of severe toxicity after CART2 (grade ≥3 cytokine release syndrome, 9%; grade ≥3 neurotoxicity, 11%). After CART2, complete response (CR) was achieved in 22% of CLL, 19% of NHL, and 21% of ALL patients. The median durations of response after CART2 in CLL, NHL, and ALL patients were 33, 6, and 4 months, respectively. Addition of fludarabine to cyclophosphamide-based lymphodepletion before the first CAR T-cell infusion (CART1) and an increase in the CART2 dose compared with CART1 were independently associated with higher overall response rates and longer progression-free survival after CART2. We observed durable CAR T-cell persistence after CART2 in patients who received cyclophosphamide and fludarabine (Cy-Flu) lymphodepletion before CART1 and a higher CART2 compared with CART1 cell dose. The identification of 2 modifiable pretreatment factors independently associated with better outcomes after CART2 suggests strategies to improve in vivo CAR T-cell kinetics and responses after repeat CAR T-cell infusions, and has implications for the design of trials of novel CAR T-cell products after failure of prior CAR T-cell immunotherapies.</jats:p>","journal":"Blood","year":2021,"id":620383,"datarank":0.8069846030310691,"base_score":5.37989735354046,"endowment":5.37989735354046,"self_citation_contribution":0.8069846030310691,"citation_network_contribution":0.0,"self_endowment_contribution":0.8069846030310691,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":216,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":464928,"name":"Evandro D. 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We analyzed data from 44 patients with R/R B-cell malignancies (acute lymphoblastic leukemia [ALL], n = 14; chronic lymphocytic leukemia [CLL], n = 9; non-Hodgkin lymphoma [NHL], n = 21) who received CART2 on a phase 1/2 trial (NCT01865617) at our institution. Despite a CART2 dose increase in 82% of patients, we observed a low incidence of severe toxicity after CART2 (grade ≥3 cytokine release syndrome, 9%; grade ≥3 neurotoxicity, 11%). After CART2, complete response (CR) was achieved in 22% of CLL, 19% of NHL, and 21% of ALL patients. The median durations of response after CART2 in CLL, NHL, and ALL patients were 33, 6, and 4 months, respectively. Addition of fludarabine to cyclophosphamide-based lymphodepletion before the first CAR T-cell infusion (CART1) and an increase in the CART2 dose compared with CART1 were independently associated with higher overall response rates and longer progression-free survival after CART2. We observed durable CAR T-cell persistence after CART2 in patients who received cyclophosphamide and fludarabine (Cy-Flu) lymphodepletion before CART1 and a higher CART2 compared with CART1 cell dose. The identification of 2 modifiable pretreatment factors independently associated with better outcomes after CART2 suggests strategies to improve in vivo CAR T-cell kinetics and responses after repeat CAR T-cell infusions, and has implications for the design of trials of novel CAR T-cell products after failure of prior CAR T-cell immunotherapies.</jats:p>","is_dataset_classified":null,"base_score":5.37989735354046,"endowment":5.37989735354046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32967009","pmcid":"PMC7819764","openalex_id":"https://openalex.org/W3088453061","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"T32 HL007093","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA136551","title":null},{"funder_name":"NCI NIH HHS","grant_id":"K12 CA076930","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK056465","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA015704","title":null}],"total_grants":5,"fwci":9.5741,"citation_percentile":0.98664963,"influential_citations":0,"citation_trend":[{"year":2020,"count":1},{"year":2021,"count":30},{"year":2022,"count":35},{"year":2023,"count":55},{"year":2024,"count":50},{"year":2025,"count":30},{"year":2026,"count":15}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://ashpublications.org/blood/article-pdf/137/3/323/1797674/bloodbld2020006770.pdf","host_type":"journal"},{"url":"https://ashpublications.org/blood/article-pdf/137/3/323/1797674/bloodbld2020006770.pdf","host_type":"publisher"},{"url":"http://ashpublications.org/blood/article-pdf/137/3/323/1797674/bloodbld2020006770.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1182/blood.2020006770","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32967009","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7819764","host_type":"repository"}],"fields_of_study":["CAR-T cell therapy research","Advancements in Semiconductor Devices and Circuit Design","Nanowire Synthesis and Applications","Adult","Aged","Antigens, CD19","Cell Proliferation","Cyclophosphamide","Cytokine Release Syndrome","Female","Humans","Immunotherapy, Adoptive","Leukemia, B-Cell","Leukemia, Lymphocytic, Chronic, B-Cell","Lymphoma, Non-Hodgkin","Male","Middle Aged","Multivariate Analysis","Precursor Cell Lymphoblastic Leukemia-Lymphoma","Progression-Free Survival","T-Lymphocytes","Treatment Outcome","Vidarabine"],"mesh_terms":["Progression-Free Survival","Cytokine Release Syndrome","Adult","Aged","Cyclophosphamide","Female","Humans","Lymphoma, Non-Hodgkin","Male","Middle Aged","T-Lymphocytes","Vidarabine","Leukemia, B-Cell","Leukemia, Lymphocytic, Chronic, B-Cell","Multivariate Analysis","Immunotherapy, Adoptive","Treatment Outcome","Antigens, CD19","Cell Proliferation","Precursor Cell Lymphoblastic Leukemia-Lymphoma"],"keywords":["Fludarabine","Medicine","Cytokine release syndrome","Cyclophosphamide","Chronic lymphocytic leukemia","Internal medicine","Lymphoma","CD19","Immunology","Gastroenterology","Oncology","T cell","Leukemia","Chemotherapy","Chimeric antigen receptor","Antigen","Immune system"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T10:54:50.246385Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}