{"doi":"10.1016/j.jtct.2023.06.019","title":"Chimeric Antigen Receptor T Cells as Salvage Therapy for Post-Chimeric Antigen Receptor T Cell Failure","abstract":"ABSTRACT Outcomes for post-chimeric antigen receptor (CAR) T cell therapy (CART) relapse are poor. The utilization of a unique CAR T cell construct for post-CART failure is increasing, but this approach is not well described. In this study, with CART-A the first unique CAR T cell construct received and CART-B the second, the primary objective was to characterize outcomes following CART-B. Secondary objectives included evaluating safety and toxicity with sequential CART infusions; investigating the impact of potential factors, such as antigen modulation and interval therapy, on CART-B response; and characterizing long-term outcomes in patients receiving multiple CARTs. This was a retrospective review (NCT03827343) of children and young adults with B cell acute lymphoblastic leukemia (B-ALL) undergoing CART therapy who received at least 2 unique CART constructs, excluding interim CART reinfusions of the same product. Of 135 patients, 61 (45.1%) received 2 unique CART constructs, including 13 who received >2 CARTs over time. Patients included in this analysis received 14 distinct CARTs targeting CD19 and/or CD22. The median age at CART-A was 12.6 years (range, 3.3 to 30.4 years). The median time from CART-A to CART-B was 302 days (range, 53 to 1183 days). CART-B targeted a different antigen than CART-A in 48 patients (78.7%), owing primarily to loss of CART-A antigen target. The rate of complete remission (CR) was lower with CART-B (65.5%; 40 of 61) than with CART-A (88.5%; 54 of 61; P = .0043); 35 of 40 (87.5%) CART-B responders had CART-B targeting a different antigen than CART-A. Among the 21 patients with a partial response or nonresponse to CART-B, 8 (38.1%) received CART-B with the same antigen target as CART-A. Of 40 patients with CART-B complete response (CR), 29 (72.5%) relapsed. For the 21 patients with evaluable data, the relapse immunophenotype was antigen negative in 3 (14.3%), antigen dim in 7 (33.3%), antigen positive in 10 (47.6%), and lineage switch in 1 (4.8%). The median relapse-free survival following CART-B CR was 9.4 months (95% confidence interval [CI], 6.1 to 13.2 months), and overall survival was 15.0 months (95% CI, 13.0 to 22.7 months). Given the limited salvage options for post-CART relapse, identifying optimizing strategies for CART-B is critical. We raise awareness about the emerging use of CART for post-CART failure and highlight clinical implications accompanying this paradigm shift.","journal":"Transplantation and Cellular Therapy","year":2023,"id":371341,"datarank":0.3703299063948744,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.07844338403657733,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.07844338403657733,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":5,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03827343"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":283310,"name":"Bonnie Yates","orcid":null,"position":1,"is_corresponding":false},{"id":109203,"name":"Seth M. Steinberg","orcid":"0000-0002-8280-551X","position":2,"is_corresponding":false},{"id":278259,"name":"Constance M. Yuan","orcid":"0000-0002-2601-3665","position":3,"is_corresponding":false},{"id":334817,"name":"Hao‐Wei Wang","orcid":"0000-0002-5408-9253","position":4,"is_corresponding":false},{"id":651129,"name":"Colleen Annesley","orcid":"0000-0002-3473-0947","position":5,"is_corresponding":false},{"id":280937,"name":"Haneen Shalabi","orcid":"0000-0001-8692-8034","position":6,"is_corresponding":false},{"id":233604,"name":"David F. Stroncek","orcid":"0000-0001-5867-3265","position":7,"is_corresponding":false},{"id":309028,"name":"Terry J. Fry","orcid":"0000-0001-8044-5226","position":8,"is_corresponding":false},{"id":1130955,"name":"Joerg Krueger","orcid":"0000-0003-1225-1977","position":9,"is_corresponding":false},{"id":883466,"name":"Elad Jacoby","orcid":"0000-0003-1411-8942","position":10,"is_corresponding":false},{"id":612971,"name":"Emily M. Hsieh","orcid":"0000-0001-5088-7621","position":11,"is_corresponding":false},{"id":262386,"name":"Deepa Bhojwani","orcid":"0000-0002-7559-7927","position":12,"is_corresponding":false},{"id":487066,"name":"Rebecca Gardner","orcid":"0000-0003-1532-3200","position":13,"is_corresponding":false},{"id":632643,"name":"Shannon L. Maude","orcid":"0000-0003-2210-8736","position":14,"is_corresponding":false},{"id":280941,"name":"Nirali N. Shah","orcid":"0000-0002-8474-9080","position":15,"is_corresponding":false},{"id":654395,"name":"Elizabeth M. Holland","orcid":null,"position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T01:15:45.330525Z","pmid":"37394115","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":[]}