biostudies-literatureUnknown14Springer CIn myeloma patients, high levels of soluble BCMA (sBCMA) can limit the efficacy of BCMA-directed therapies. Belantamab-mafodotin is a BCMA antibody-drug conjugate and shows good overall response rates in heavily pretreated patients but progression-free survival data are poor. As the drug induces apoptosis, we hypothesized that sBCMA includes extracellular vesicles (EV) and thus evaluated numbers of BCMA-EV before and during belantamab therapy in 10 myeloma patients. BCMA-EV were significantly higher in patients prior to Belantamab (median: 3227/μl; <i>p</i> = .013) than in other myeloma patients before therapy (<i>n</i> = 10; 1082/μl) or healthy volunteers (<i>n</i> = 10; 980/μl). During therapy, BCMA-EV showed a significant increase to a maximum of 8292/μl (<i>p</i> = .028). Maximal changes in BCMA-EV (Δmax = BCMA-EV at C1/maximal BCMA-EV) showed a strong inverse, logarithmic correlation (r = -.950; <i>p</i> < .001) with FLC ratio changes (Δmax = FLC ratio at C1/minimal FLC ratio) and BCMA-EV peaks often preceded FLC progression. Correlating increase of LDH and BCMA-EV levels, together with clinical symptoms, point to a mafodotin-induced eryptosis. In summary, BCMA-EV are a part of sBCMA, peak levels precede progression, and their measurement might be helpful in identifying resistance mechanisms and side effects of BCMA targeted therapies.Oncotarget949-956https://www.ebi.ac.uk/biostudies/studies/S-EPMC10691812biostudies-literaturePlasma levels of BCMA-positive extracellular vesicles correlate to response and side effects in myeloma patients treated with belantamab-mafodotin.PMC10691812Trummer AKrauter JSpringer CfalsePlasma levels of BCMA-positive extracellular vesicles correlate to response and side effects in myeloma patients treated with belantamab-mafodotin.In myeloma patients, high levels of soluble BCMA (sBCMA) can limit the efficacy of BCMA-directed therapies. Belantamab-mafodotin is a BCMA antibody-drug conjugate and shows good overall response rates in heavily pretreated patients but progression-free survival data are poor. As the drug induces apoptosis, we hypothesized that sBCMA includes extracellular vesicles (EV) and thus evaluated numbers of BCMA-EV before and during belantamab therapy in 10 myeloma patients. BCMA-EV were significantly higher in patients prior to Belantamab (median: 3227/μl; <i>p</i> = .013) than in other myeloma patients before therapy (<i>n</i> = 10; 1082/μl) or healthy volunteers (<i>n</i> = 10; 980/μl). During therapy, BCMA-EV showed a significant increase to a maximum of 8292/μl (<i>p</i> = .028). Maximal changes in BCMA-EV (Δmax = BCMA-EV at C1/maximal BCMA-EV) showed a strong inverse, logarithmic correlation (r = -.950; <i>p</i> < .001) with FLC ratio changes (Δmax = FLC ratio at C1/minimal FLC ratio) and BCMA-EV peaks often preceded FLC progression. Correlating increase of LDH and BCMA-EV levels, together with clinical symptoms, point to a mafodotin-induced eryptosis. In summary, BCMA-EV are a part of sBCMA, peak levels precede progression, and their measurement might be helpful in identifying resistance mechanisms and side effects of BCMA targeted therapies.2023-01-01T00:00:00Z2023 Dec2025-04-25T17:24:10.706Z2025-04-06T04:05:30.451ZS-EPMC106918123803941410.18632/oncotarget.28538