Background Multiple myeloma (MM) is the second most common hematologic malignancy. In recent years, the introduction of several novel agents has markedly improved treatment outcomes; however, MM remains incurable and patients inevitably relapse. After multiple relapses, therapeutic options become increasingly limited. Immunotherapy has recently emerged as a new avenue for MM patients, with chimeric antigen receptor T-cell (CAR-T) therapy currently attracting the greatest attention.

This single-center, retrospective study included all 29 patients with relapsed/refractory MM (RRMM) who received BCMA-directed CAR-T therapy while hospitalized in the Department of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine, between January 2018 and November 2024. Eleven of these patients (37.9%) harbored high-risk cytogenetic abnormalities, including 1q amplification, del(17p), and 14q rearrangements. All diagnoses were confirmed according to the International Myeloma Working Group (IMWG) criteria.

Baseline characteristics Every patient had received induction therapy containing at least three classes of novel agents: proteasome inhibitor (PI)-based regimens, immunomodulatory drug (IMiD)-based regimens, PI + IMiD combinations, and CD38 monoclonal antibodies. Response assessment followed IMWG criteria.Among the 29 RRMM patients with 1q amplification, TP53 abnormalities, or 14q rearrangements, 14 (48.3%) were male, 15 (51.7%) were ≥ 60 years old, 17 (58.6%) were Durie-Salmon stage III, and 6 (20.7%) were ISS stage III. IgG was the predominant M-protein subtype in 15 patients (51.7%). Regarding prior therapy, all 29 had received PI-based regimens, 22 (75.9%) had received PI + IMiD combinations, and 15 (51.7%) had progressed after prior CD38 antibody exposure. Six (20.7%) had relapsed after autologous hematopoietic stem-cell transplantation (auto-HSCT). Seven patients (24.1%) had received ≥ 4 prior lines of therapy (median 3; range 2–6).

Bone marrow samples were subjected to fluorescence in situ hybridization (FISH) using probes targeting TP53 (17p13.1), 1q21, IGH/MAF (14q32/16q23), IGH/FGFR3 (14q32/4p16.3), and IGH/CCND1 (14q32/11q13). Two hundred interphase nuclei were scored for each probe; the laboratory-defined cut-off values determined positivity.

Follow-up Follow-up data were extracted from the electronic medical record system. The last follow-up date was 31 March 2025; the median follow-up duration was 38.0 months（8.0-84.0m）. Overall survival (OS) was measured from CAR-T infusion to death from any cause or last contact. Progression-free survival (PFS) was measured from infusion to disease progression or death from any cause.

Results The twenty-nine enrolled RRMM patients had been heavily pre-treated with PIs, IMiDs, CD38 antibodies, and six had undergone auto-HSCT. Four were ISS/R-ISS stage III .Six patients had extramedullary disease, as an ultra-high-risk cohort with extremely poor prognosis. After BCMA CAR-T infusion, 28/29 responded, 15 achieving sCR; all responding patients became MRD-negative without additional therapy. Median PFS was 29.2 months and median OS was 36.7 months,even for the patients of PS score 4.One patient has maintained sCR for 61 months.

MRD was assessed in patients achieving complete response (CR). Among 29 patients who attained stringent CR (sCR) or CR, 15 (51.7%) became MRD-negative. The overall response rate (≥ very good partial response, VGPR) was 89.7% (26/29). Of the twelve patients with more than two high-risk factors, six patients achieved MRD negativity.

Any-grade cytokine-release syndrome (CRS) occurred in 18/29 patients; The patients of more than 3 grade were observed in 3 cases (10%) and resolved with supportive treatment. One patient developed immune-effector-cell associated neurotoxicity syndrome (ICANS) and fully recovered after treatment. Cytopenias of 3 grade occurred in 9 patients (31.0%) and were reversible.

Conclusions This single-center retrospective analysis of 29 RRMM patients treated with BCMA CAR-T, and the longest follow-up time to 7 years. In our study,the high burden MM patients got sCR will achieve long-term survival without maintenance therapy.

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2025
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