{"doi":"10.1002/hon.70094_413","title":"413 | PROGRESSION PATTERNS BY POSITRON EMISSION TOMOGRAPHY FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA AFTER CAR T CELL THERAPY: POTENTIAL ROLE FOR RADIOTHERAPY?","abstract":"Background: Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable efficacy in MM. However, many patients (pts) have incomplete and non-durable responses. We characterized post-CAR T progression for RRMM, using PET to identify high risk lesions that may benefit from bridging RT prior to CAR T. Methods: We analyzed 71 MM pts treated between 2017 and 2022 with BCMA-directed CAR T (38 experimental, 33 commercial products). A total of 529 FDG-avid lesions on pre-CAR T PET (pre-apheresis if bridging therapy, pre-lymphodepleting chemotherapy if no bridging), and 321 lesions on post-CAR T PET at first failure were categorized, with failure defined as radiologic and/or serologic progression according to Lugano and International Myeloma Working Group criteria, respectively. At the pt level, we classified disease as osseous (O), extramedullary (EM) / paramedullary (PM), or mixed O and EM/PM. Individual lesions were classified as O, EM, or PM. Lesions were also classified as progressive, stable, or new at pre-CAR T PET according to SUV change from preceding PET. Failure of a lesion present on pre-CAR T PET was defined as progression involving the same anatomic structure and within 3 cm from initial lesion. Pearson’s X2 test was used to compare pre- and post-CART PET. Kaplan-Meier curves for progression-free survival (PFS) were constructed. Results: Pre-CAR T PET was performed at median 1.4 months (range, 0.2–8.5) prior to CAR T, with 27 (39%) pts receiving systemic bridging, 10 (14%) RT +/− systemic, and 32 (46%) none. Median number of PET avid sites pre-CAR T was 6 (0–9) per pt. Of the 71 pts, 34 (53%) had mixed O and EM/PM, 24 (37%) O only, and 6 (10%) EM/PM only; 7 (10%) had no lesions. Of the 529 lesions on pre-CAR T PET, 351 (66%) were O, 131 (25%) EM, and 47 (9%) PM. A total of 61 (86%) pts progressed post-CAR T (median time to progression of 6 months (interquartile range: 2–11)), 28 (46%) of whom had first failure in new and pre-existing sites, 17 (20%) in new sites only, 6 (10%) in pre-existing sites only, and 10 (16%) serologically only. At the lesion level, 101/321 (31%) failures occurred in lesions on pre-CAR T PET. At failure, EM (44% vs. 25%) and PM (12% vs. 9%) lesions made up a higher percentage of all lesions compared to pre-CAR T (p < 0.001). Of the initial 529 lesions, failure occurred in 44/131 (34%) EM, 16/47 (34%) PM, and 41/351 (12%) O sites (p < 0.001). Lesions progressing at time of pre-CAR T PET failed more frequently (41/143, 29%) than those that were stable (20/130, 15%) or new (24/175, 14%) (p = 0.002). PFS was worse in pts with EM disease (p < 0.001) and > 3 lesions (p = 0.037) pre-CART. Conclusion: EM and PM sites progressed locally at higher rates than O sites, as did progressive lesions pre-CAR T. PFS was worse in EM/PM sites, suggesting higher risk lesion characteristics for which targeted RT cytoreduction may be beneficial. Further analysis could inform integrating selective site RT pre-CAR T as a bridging intervention. Research funding declaration: None Keywords: cellular therapies; cellular therapies; radiation therapy No potential sources of conflict of interest.","journal":"Hematological Oncology","year":2025,"id":568598,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9427,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":554294,"name":"Harper Hubbeling","orcid":"0000-0003-4812-5235","position":1,"is_corresponding":false},{"id":1473757,"name":"B. Fregonese","orcid":null,"position":2,"is_corresponding":false},{"id":291177,"name":"G. Cederquist","orcid":"0000-0003-4749-6093","position":3,"is_corresponding":false},{"id":1090533,"name":"Nikhil P. Mankuzhy","orcid":"0000-0001-9004-7598","position":4,"is_corresponding":false},{"id":267640,"name":"Roshal R. Patel","orcid":"0000-0002-6117-5520","position":5,"is_corresponding":false},{"id":414609,"name":"Kaitlyn Lapen","orcid":"0000-0002-3193-7950","position":6,"is_corresponding":false},{"id":878449,"name":"Zachary Moore","orcid":"0000-0002-7839-7250","position":7,"is_corresponding":false},{"id":432851,"name":"Hamza Hashmi","orcid":"0000-0002-4129-5867","position":8,"is_corresponding":false},{"id":1473758,"name":"S. Mailankody","orcid":null,"position":9,"is_corresponding":false},{"id":268260,"name":"Saad Z. Usmani","orcid":"0000-0002-5484-8731","position":10,"is_corresponding":false},{"id":1473759,"name":"J. Yahalom","orcid":null,"position":11,"is_corresponding":false},{"id":363895,"name":"Brandon S. Imber","orcid":"0000-0002-1281-5915","position":12,"is_corresponding":false},{"id":659610,"name":"Alexandra Dreyfuss","orcid":"0000-0002-3335-3094","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:55.795846Z","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":[]}