{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:49:59Z","timestamp":1791352199726,"version":"4.3.1"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Richter transformation (RT) that relapses after CD19-directed chimeric antigen receptor (CAR) T-cell therapy has no established therapy and carries a dismal prognosis. We report an 84-year-old man with multiply relapsed, biopsy-proven diffuse large B-cell lymphoma-type RT and a high-risk MYC\/BCL2 double-expressor phenotype who developed systemic relapse, with extensive osteolytic bone disease, after lisocabtagene maraleucel. Three cycles of atezolizumab produced no objective benefit. Treatment with epcoritamab, a CD3xCD20 bispecific antibody, plus pirtobrutinib, a non-covalent Bruton tyrosine kinase inhibitor, produced complete nodal metabolic resolution within 3 months that deepened to a complete metabolic response (Deauville score 2) by 10 treatment cycles, with resolution of two interim osteolytic lesions whose transient nature illustrates the interpretive challenges of PET\/CT response assessment after cellular and T-cell-engaging therapies. The chemotherapy-free regimen was well tolerated at age 84, with no cytokine release syndrome, no neurotoxicity, and no cytopenias; the only toxicity was mild, reversible dexamethasone-related myopathy. The patient remains in ongoing clinical remission after approximately 10 months of therapy. This case extends the reported experience with epcoritamab plus pirtobrutinib specifically to the post-CAR T-cell relapse setting and suggests that this chemotherapy-free doublet may warrant consideration as a salvage strategy for older or frail patients with RT who are unfit for further cytotoxic therapy.<\/jats:p>","DOI":"10.3389\/fmed.2026.1998014","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:52:17Z","timestamp":1791348737000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Durable, well-tolerated complete response to epcoritamab plus pirtobrutinib in Richter transformation relapsing after CD19 CAR T-cell therapy"],"prefix":"10.3389","volume":"13","author":[{"given":"Ahmed Salleh","family":"Barefah","sequence":"first","affiliation":[{"name":"Hematology Department, Faculty of Medicine, King Abdulaziz University Hospital, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]},{"name":"Hematology Research Unit, King Fahad Medical Research Center, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1182\/blood-2018-01-791376","article-title":"Biology and treatment of Richter syndrome","volume":"131","author":"Rossi","year":"2018","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1182\/blood.2024028064","article-title":"International consensus statement on diagnosis, evaluation, and research of Richter transformation: the ERIC recommendations","volume":"146","author":"Kittai","year":"2025","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1200\/JCO.24.00033","article-title":"Anti-CD19 chimeric antigen receptor 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