{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T02:02:00Z","timestamp":1783044120834,"version":"3.54.6"},"reference-count":132,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"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. Immunol."],"abstract":"<jats:p>Chimeric antigen receptor (CAR) cellular therapies have advanced outcomes in challenging hematologic malignancies like leukemia, lymphoma, and multiple myeloma. Plasma cell-directed CAR T-cell therapies have been particularly beneficial in multiple myeloma, suggesting that these agents may have a role in other challenging plasma cell disorders such as systemic AL amyloidosis and plasma cell leukemia. AL amyloidosis is a monoclonal plasma cell disorder resulting in the deposition of protein fibrils that compromise end-organ function. Delays in diagnosis can result in end-organ dysfunction and organ failure, making designing and completing treatment difficult. Plasma cell leukemia (PCL) is a rare and highly challenging malignancy with dismal survival outcomes despite aggressive therapy. Both diagnoses are currently treated with regimens borrowed from myeloma: a combination of novel agents and chemotherapy induction, then autologous stem cell transplantation (ASCT), with the current practice trending towards consolidation and maintenance. Unfortunately, only 20% of AL amyloidosis patients are transplant-eligible at diagnosis. Those transplant-ineligible (TIE) patients are treated with combination induction chemotherapy, which may be limited by worsening disease-related end-organ dysfunction. Plasma cell leukemia patients are still very likely to relapse after this intensive and prolonged therapy. Despite the promise of a shorter course of therapy, CAR T-cell therapies directed against plasma cells have not been rigorously investigated in patients with AL amyloidosis or PCL; most trials of MM have excluded these patients. Herein, we describe current treatment paradigms for AL amyloidosis and PCL and review the evidence for CAR T-cell therapies in these challenging plasma cell disorders. Further investigation into CAR T-cell therapies for plasma cell disorders other than multiple myeloma is warranted.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1558275","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T06:26:54Z","timestamp":1744093614000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Changing lanes: extending CAR T-cell therapy to high-risk plasma cell dyscrasias"],"prefix":"10.3389","volume":"16","author":[{"given":"Heather T.","family":"Morgan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A.","family":"Derman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaji 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