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In myeloma patients, high levels of soluble B-cell maturation antigen (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. In this new study, researchers Carsten Springer, Jürgen Krauter and Arne Trummer,from Städtisches Klinikum Braunschweig and Heidekreis-Klinikum in Germany, investigated whether sBCMA in blood plasma includes extracellular vesicles (EV) carrying BCMA or other myeloma antigens and if these BCMA-EV levels show a significant change during therapy with belantamab-mafodotin.
“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; p = .013) than in other myeloma patients before therapy (n = 10; 1082/μl) or healthy volunteers (n = 10; 980/μl). During therapy, BCMA-EV showed a significant increase to a maximum of 8292/μl (p = .028). Maximal changes in BCMA-EV (Δmax = BCMA-EV at C1/maximal BCMA-EV) showed a strong inverse, logarithmic correlation (r = −.950; p < .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.
“To the best of our knowledge, we demonstrate for the first time that BCMA-positive extracellular vesicles can be found in blood plasma from myeloma patients and that BCMA expression on EV is 10 to 100 times higher than that of other well-known antigens of myeloma cells.”
Keywords: myeloma, b cell maturation antigen, extracellular vesicles, belantamab-mafodotin, eryptosis
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open-access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
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