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Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial

Autores: Puig, N. ; Corchete-Sanchez, L. A. ; Perez-Moran, J. J. ; Davila, J. ; Paino, T. ; de la Rubia, J. ; Oriol, A. ; Martin-Sanchez, J. ; de Arriba, F. ; Blad, J. ; Blanchard, M. J. ; Gonzalez-Calle, V. ; Garcia-Sanz, R. ; Paiva, B. ; Lahuerta, J. J. ; San Miguel Izquierdo, Jesús; Mateos, M. V. ; Ocio, E. M. (Autor de correspondencia)
Título de la revista: CANCERS
ISSN: 2072-6694
Volumen: 12
Número: 12
Páginas: 3615
Fecha de publicación: 2020
Simple Summary Multiple myeloma patients with persistent disease after treatment show increased expression of PDL1 in tumor plasma cells and of PD1 in T lymphocytes. This suggests a role of the PD1/PDL1 axis in treatment failure that could potentially be reverted with pembrolizumab, an anti-PD1 monoclonal antibody. The GEM-Pembresid trial enrolled 20 patients with multiple myeloma achieving a suboptimal response to the previous treatment that received intravenous pembrolizumab every 3 weeks with the objective of eradicating the residual disease. Pembrolizumab was acceptably well tolerated in the 17 patients evaluable for safety, but no improvement in the baseline responses was documented. Although no determinants of response could be identified, we detected a lower expression of PD1/PDL1 in a subgroup of patients progressing in the first 4 months after enrollment; furthermore, a reduction in the percentage of NK cells induced by pembrolizumab was observed. 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 with identifier NCT02636010 and with EUDRACT number 2015-003359-23.