학술논문
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
Document Type
article
Author
Rao Prabhala; William E. Pierceall; Mehmet Samur; Lakshmi B. Potluri; Kevin Hong; Teresa Peluso; Srikanth Talluri; Angela Wang; Aishwarya Katiki; Sahan D. Vangala; Michael Buonopane; Vaishnavi Bade; Hannah Seah; Arthur Krogman; Sanika Derebail; Mariateresa Fulciniti; Suzan B. Lazo; Paul Richardson; Kenneth Anderson; Jill Corre; Herve Avet-Loiseau; Anjan Thakurta; Nikhil Munshi
Source
Frontiers in Oncology, Vol 13 (2023)
Subject
Language
English
ISSN
2234-943X
Abstract
BackgroundMultiple 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.MethodsWe 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.ResultsAmong 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