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Richter transformation is still a serious risk in the era of innovative therapies, despite the fact that targeted therapy with Bruton's tyrosine kinase inhibitor has significantly improved the prognosis for chronic lymphocytic leukemia (CLL). We report a rare case of a 61-year-old male patient's CLL transforming into a synchronous clonal related plasmablastic lymphoma (PBL) after receiving ibrutinib. During COVID-19, the patient stopped taking ibrutinib, which caused the illness to worsen. Histology revealed that PBL was present in the right supraclavicular mass and that CLL had penetrated the bone marrow. Three cycles of CHP (cyclophosphamide, doxorubicin, and prednisone) were administered together with venetoclax and brentuximab vedotin. After receiving BCMA CAR-T cell treatment, the patient was in complete remission. For PBL transformation, a condition with a worse prognosis and few therapy choices, our results suggest the use of BCMA CAR-T and novel target agents.
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http://dx.doi.org/10.1016/j.critrevonc.2024.104551 | DOI Listing |
Eur J Haematol
September 2025
Department of Hematology-Oncology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapies have revolutionized the approach and management of relapsed/refractory multiple myeloma (RRMM), and as of 2025, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are the only BCMA-targeted CAR T-cell therapies approved by the FDA. Exceptional responses were demonstrated for heavily pretreated patients in the KarMMa-1 trial, reporting a 73% overall response rate (ORR) and 98% in the CARTITUDE-1 trial. Furthermore, both therapies show a significant improvement in progression-free survival (PFS) compared to standard regimens when administered in earlier lines.
View Article and Find Full Text PDFAnn Hematol
September 2025
Excellence Center for Comprehensive Cancer (ECCCC), King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Despite therapeutic advances, multiple myeloma (MM) remains incurable, especially in relapsed/refractory (R/R) cases. B-cell maturation antigen (BCMA) is a key target for novel immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific T-cell engagers (BiTEs), which vary in efficacy, toxicity, and accessibility. To compare the efficacy and safety of BCMA-directed CAR-T therapies and BiTEs in R/R MM through a systematic review and meta-analysis.
View Article and Find Full Text PDFOncoimmunology
December 2025
Department for Cell and Gene Therapy Development, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
CAR-based cell therapies have shown clinical success in treating various cancers, with CAR T cell therapies entering the clinical route and CAR NK cell therapies being evaluated in early-stage clinical trials. A key challenge is the presence of tumor-associated antigens on healthy cells, risking on-target off-tumor toxicities. Our comparative analysis of CAR T and CAR NK cells targeting the multiple myeloma-associated antigens BCMA, SLAMF7, and CD38 revealed that antigen density on target cells significantly modulates CAR NK cell activation and cytotoxicity.
View Article and Find Full Text PDFBlood Cancer Discov
September 2025
Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Genomic antigen loss is a recurring mechanism of resistance to chimeric antigen receptor T-cell (CAR-T) and T-cell engagers (TCE) in relapsed/refractory multiple myeloma (RRMM). Yet, it remains unclear whether these events are acquired under treatment or merely selected from pre-existing, undetectable clones. By leveraging chemotherapy mutational signatures as temporal barcodes within whole genome sequencing data, we could time genomic antigen escape in 4 out of 11 RRMM patients.
View Article and Find Full Text PDFZ Rheumatol
September 2025
Medizinische Klinik V (Hämatologie, Onkologie und Rheumatologie), Deutsches Konsortium für Tumorerkrankungen (DKTK) und Nationales Zentrum für Tumorerkrankungen (NCT), Universitätsklinikum Heidelberg (UKHD), Im Neuenheimer Feld 410, 69120, Heidelberg, Deutschland.
The targeted and personalized cell and gene therapy with autologous chimeric antigen receptor (CAR) transduced T‑cells (CAR T‑cells) has become established as the standard therapy for patients with B‑cell diseases, such as CD-19 positive leukemia and lymphomas and B‑cell maturation antigen (BCMA) positive multiple myeloma (MM). This therapy has been approved in Europe since 2018 and is administered in more than 50 clinics in Germany. With increasing experience and expertise in understanding of the principles of action and underlying mechanisms as well as mitigation of side effects have significantly improved.
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