BCMA+ EV Levels Correlate With Myeloma Response to Belantamab-Mafodotin

“Measurement of BCMA-EV can thus help in identifying resistance mechanisms and side effects of BCMA targeted therapies in future studies.”

BUFFALO, NY- December 6, 2023 – A new research paper was published in Oncotarget's Volume 14 on December 1, 2023, entitled, “Plasma 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 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.”

Read the full paper: DOI: https://doi.org/10.18632/oncotarget.28538 

Correspondence to: Arne Trummer

Email: arne.trummer@heidekreis-klinikum.de 

Keywords: myeloma, b cell maturation antigen, extracellular vesicles, belantamab-mafodotin, eryptosis

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