B cell maturation antigen (BCMA) is a target for various immunotherapies and a biomarker for tumor load in multiple myeloma (MM). We report a case of irreversible BCMA loss in a patient with MM who was enrolled in the KarMMa trial (NCT03361748) and progressed after anti-BCMA CAR T cell therapy. We identified selection of a clone with homozygous deletion of TNFRSF17 (BCMA) as the underlying mechanism of immune escape. Furthermore, we found heterozygous TNFRSF17 loss or monosomy 16 in 37 out of 168 patients with MM, including 28 out of 33 patients with hyperhaploid MM who had not been previously treated with BCMA-targeting therapies, suggesting that heterozygous TNFRSF17 deletion at baseline could theoretically be a risk factor for BCMA loss after immunotherapy.
Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma / M.C. Da Vià, O. Dietrich, M. Truger, P. Arampatzi, J. Duell, A. Heidemeier, X. Zhou, S. Danhof, S. Kraus, M. Chatterjee, M. Meggendorfer, S. Twardziok, M.-. Goebeler, M.S. Topp, M. Hudecek, S. Prommersberger, K. Hege, S. Kaiser, V. Fuhr, N. Weinhold, A. Rosenwald, F. Erhard, C. Haferlach, H. Einsele, K.M. Kortum, A.-. Saliba, L. Rasche. - In: NATURE MEDICINE. - ISSN 1078-8956. - 27:4(2021), pp. 616-619. [10.1038/s41591-021-01245-5]
Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma
M.C. Da ViàPrimo
;
2021
Abstract
B cell maturation antigen (BCMA) is a target for various immunotherapies and a biomarker for tumor load in multiple myeloma (MM). We report a case of irreversible BCMA loss in a patient with MM who was enrolled in the KarMMa trial (NCT03361748) and progressed after anti-BCMA CAR T cell therapy. We identified selection of a clone with homozygous deletion of TNFRSF17 (BCMA) as the underlying mechanism of immune escape. Furthermore, we found heterozygous TNFRSF17 loss or monosomy 16 in 37 out of 168 patients with MM, including 28 out of 33 patients with hyperhaploid MM who had not been previously treated with BCMA-targeting therapies, suggesting that heterozygous TNFRSF17 deletion at baseline could theoretically be a risk factor for BCMA loss after immunotherapy.File | Dimensione | Formato | |
---|---|---|---|
s41591-021-01245-5.pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
5.9 MB
Formato
Adobe PDF
|
5.9 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.