Paino, T. (Teresa)

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    Pembrolizumab as consolidation strategy in patients with multiple myeloma: Results of the GEM-Pembresid clinical trial
    (MDPI AG, 2020) Paino, T. (Teresa); Gonzalez-Calle, V. (Veronica); Blanchard, M.J. (María Jesús); Pérez-Morán, J. (José); Bladé, J. (Joan); García-Sanz, R. (Ramón); Ocio, E.M. (Enrique M.); Mateos, M.V. (María Victoria); Dávila, J. (Julio); Arriba, F. (Felipe) de; Puig, N. (Noemí); Lahuerta, J.J. (Juan José); Paiva, B. (Bruno); Corchete-Sánchez, L.A. (Luis A.); Oriol, A. (Albert); Rubia, J. (Javier) de la; Martín-Sánchez, J. (Jesús); San-Miguel, J.F. (Jesús F.)
    PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8+ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23.
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    Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines
    (Public Library of Science, 2014) Paino, T. (Teresa); Krzeminski, P. (Patryk); Garayoa, M. (Mercedes); Sarasquete, M.E. (María E.); García-Sanz, R. (Ramón); Ocio, E.M. (Enrique M.); San-Segundo, L. (Laura); Gutierrez, N.C. (Norma C.); Paiva, B. (Bruno); Redondo, A. M. (Alba M.); Corchete, L.A. (Luis A.); San-Miguel, J.F. (Jesús F.)
    Despite recent advances in the treatment of multiple myeloma (MM), it remains an incurable disease potentially due to the presence of resistant myeloma cancer stem cells (MM-CSC). Although the presence of clonogenic cells in MM was described three decades ago, the phenotype of MM-CSC is still controversial, especially with respect to the expression of syndecan-1 (CD138). Here, we demonstrate the presence of two subpopulations--CD138++ (95-99%) and CD138low (1-5%)--in eight MM cell lines. To find out possible stem-cell-like features, we have phenotypically, genomic and functionally characterized the two subpopulations. Our results show that the minor CD138low subpopulation is morphologically identical to the CD138++ fraction and does not represent a more immature B-cell compartment (with lack of CD19, CD20 and CD27 expression). Moreover, both subpopulations have similar gene expression and genomic profiles. Importantly, both CD138++ and CD138low subpopulations have similar sensitivity to bortezomib, melphalan and doxorubicin. Finally, serial engraftment in CB17-SCID mice shows that CD138++ as well as CD138low cells have self-renewal potential and they are phenotypically interconvertible. Overall, our results differ from previously published data in MM cell lines which attribute a B-cell phenotype to MM-CSC. Future characterization of clonal plasma cell subpopulations in MM patients' samples will guarantee the discovery of more reliable markers able to discriminate true clonogenic myeloma cells.