AUTHOR=Fang Yi , Lin Weiwei , Shen Lijing , Ni Beiwen , Zhang Minyue , Cai Yongmei , Zhou Yi , Hou Jian TITLE=First-line anti-BCMA CAR-T cell therapy in a fragile patient with biclonal gammopathy and giant plasma cell tumor multiple myeloma with multiple comorbidities: a case report JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1564774 DOI=10.3389/fimmu.2025.1564774 ISSN=1664-3224 ABSTRACT=BackgroundChimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) have been used as an effective therapy against relapsed/refractory multiple myeloma (MM). However, the relapse rates in these patients are still high, which may be related to the poor quality of T cells after multiple chemotherapies. The case reported here demonstrated the effectiveness and safety of first-line anti-BCMA CAR-T cell therapy for high-risk MM patients, even in frailty with multiple comorbidities.Case presentationA 75-year-old woman was diagnosed with biclonal gammopathy and high-risk MM with extramedullary mass in the right caput femoris. The patient was fragile with multiple comorbidities, including pneumonia, left lower limb deep venous thrombosis, and epilepsy secondary to cerebral hemorrhage. Considering the patient’s fragility and comorbidities, commercial equecabtagene autoleucel, a fully human anti-BCMA CAR-T cells, as first-line CAR-T cell therapy, was proposed and accepted by the patient and her family. After one cycle of bortezomib, cyclophosphamide, and dexamethasone (VCD) regimen), she reached very good partial response (VGPR). Then her leukapheresis was performed, and the harvested cells were sent to the manufacturer for preparation. After lymphodepletion was performed using fludarabine and cyclophosphamide (FC) chemotherapy, her equecabtagene autoleucel was transfused. On day 21 after infusion, she achieved stringent complete remission (sCR) with minimal residual disease (MRD) negativity without severe toxicity. The CAR-T cells/CD3+ T cell ratio gradually increased, reaching a maximum of 54.97% on day 14, and gradually decreased, remaining at 0.03% on the 153rd day. The patient received right hip replacement plus pelvic lesion curettage 7 months after CAR-T transfusion due to pain in her right hip, but no MM cells were found in postoperative pathology. Hitherto, her deep remission persisted for 12 months without any maintenance therapy.ConclusionFirst-line anti-BCMA CAR-T cell therapy is effective and safe for high-risk MM patients, even in fragile patients with multiple comorbidities.