Immunomodulation of NK, NKT and B/T cell subtypes in relapsed/refractory multiple myeloma patients treated with pomalidomide along with velcade and dexamethasone and its association with improved progression-free survival.

Autor:	Prabhala R; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.; VA Boston Healthcare System, Boston, MA, United States.; Harvard Medical School, Boston, MA, United States., Pierceall WE; Bristol Myers Squibb, Summit, NJ, United States., Samur M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.; Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, United States., Potluri LB; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Hong K; Bristol Myers Squibb, Summit, NJ, United States., Peluso T; Bristol Myers Squibb, Summit, NJ, United States., Talluri S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Wang A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Katiki A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Vangala SD; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Buonopane M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Bade V; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Seah H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Krogman A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Derebail S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Fulciniti M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Lazo SB; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Richardson P; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.; Harvard Medical School, Boston, MA, United States., Anderson K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.; Harvard Medical School, Boston, MA, United States., Corre J; Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France., Avet-Loiseau H; Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France., Thakurta A; Bristol Myers Squibb, Summit, NJ, United States.; Oxford Centre for Translational Myeloma Research, Oxford, United Kingdom., Munshi N; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.; VA Boston Healthcare System, Boston, MA, United States.; Harvard Medical School, Boston, MA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2023 Dec 04; Vol. 13, pp. 1271807. Date of Electronic Publication: 2023 Dec 04 (Print Publication: 2023).
DOI:	10.3389/fonc.2023.1271807
Abstrakt:	Background: Multiple Myeloma (MM) patients exhibit dysregulated immune system, which is further weakened by chemotherapeutic agents. While cereblon-modulating agents, such as pomalidomide and lenalidomide, have been found to improve the immune profile, the efficacy of their impact in combination with other treatments is yet unknown. Methods: We conducted an immune-profiling of a longitudinal cohort of 366 peripheral blood samples from the CC4047-MM-007 (OPTIMISMM, NCT01734928) study. This study followed relapsed/refractory Multiple Myeloma (RRMM) patients who were treated with Velcade + dexamethasone (Vd), or Vd with pomalidomide (PVd). 366 blood samples from 186 patients were evaluated using multi-color flow cytometry at 3 timepoints: screening, day 8 of cycle 1, and cycle 3. Results: Among NK and NKT cell populations, adding pomalidomide showed no inhibition in the frequency of NK cells. When expression of double positivity for activation markers like, p46/NKG2D, on NK cells was higher than the median, PVd treated patients showed significantly better (p=0.05) progression-free survival (PFS) (additional 15 months) than patients with lower than the median expression of p46/NKG2D on NK cells. PVd treated patients who expressed CD158a/b below the median at cycle 1 demonstrated a significantly better PFS (more than 18months). Among B cell subtypes, PVd treatment significantly increased the abundance of B1b cells (p<0.05) and decreased Bregs (p<0.05) at day 8 of both cycle 1 and cycle 3 when compared to screening samples. Of all the B cell-markers evaluated among paired samples, a higher expression of MZB cells at day 8 of cycle 1 has resulted in enhanced PFS in PVd treated patients. Within T cells, pomalidomide treatment did not decrease the frequency of CD8 T cells when compared with screening samples. The higher the surface expression of OX-40 on CD8 T cells and the lower the expression of PD-1 and CD25 on CD4 T cells by PVd treatment resulted in improved PFS. Conclusion: The prognostic significance for the number of immune markers is only seen in the PVd arm and none of these immune markers exhibit prognostic values in the Vd arm. This study demonstrates the importance of the immunomodulatory effects and the therapeutic benefit of adding pomalidomide to Vd treatment. Competing Interests: Authors WP, KH, TP, AT, were employed by the company BMS, Bristol Myers Squibb. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Prabhala, Pierceall, Samur, Potluri, Hong, Peluso, Talluri, Wang, Katiki, Vangala, Buonopane, Bade, Seah, Krogman, Derebail, Fulciniti, Lazo, Richardson, Anderson, Corre, Avet-Loiseau, Thakurta and Munshi.)
Databáze:	MEDLINE
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