title: Circulating immune cell phenotype can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma.
abstract: Although the antimyeloma effect of lenalidomide is associated with activation of the immune system, the exact in vivo immunomodulatory mechanisms of lenalidomide combined with low-dose dexamethasone (Len-dex) in refractory/relapsed multiple myeloma (RRMM) patients remain unclear. In this study, we analyzed the association between immune cell populations and clinical outcomes in patients receiving Len-dex for the treatment of RRMM. Peripheral blood samples from 90 RRMM patients were taken on day 1 of cycles 1 (baseline), 2, 3, and 4 of Len-dex therapy. Peripheral blood CD3(+), CD4(+), and CD8(+) cell frequencies were significantly decreased by 3 cycles of therapy, whereas NK cell frequency was significantly increased after the 3rd cycle. For the myeloid-derived suppressor cell (MDSC) subset, the frequency of granulocytic MDSCs transiently increased after the 1st cycle, whereas there was an increase in monocytic MDSC (M-MDSC) frequency after the 1st and 3rd cycles. Among 81 evaluable patients, failure to achieve a response of VGPR or greater was associated with a decrease in CD8(+) cell frequency and increase in M-MDSC frequency after 3 cycles of Len-dex treatment. A high proportion of natural killer T (NKT)-like cells (CD3(+)/CD56(+)) prior to Len-dex treatment might predict a longer time to progression. In addition, patients with a smaller decrease in the frequency of both CD3(+) cells and CD8(+) cells by 3 cycles exhibited a longer time to the next treatment. These results demonstrated that early changes in immune cell subsets are useful immunologic indicators of the efficacy of Len-dex treatment in RRMM.
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.
authors.forename: Da-Bin
authors.initials: DB
authors.lastname: Ryu
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.|Catholic Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea.
authors.forename: Byung-Sik
authors.initials: BS
authors.lastname: Cho
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.|Catholic Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea.
authors.forename: Ki-Seong
authors.initials: KS
authors.lastname: Eom
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.|Catholic Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.|Catholic Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hee-Je
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.|Catholic Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.
authors.forename: Seok-Goo
authors.initials: SG
authors.lastname: Cho
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.|Catholic Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea.
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Min
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Myungshin
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpodaero, Seocho-Gu, Seoul, 06591, Korea. ckmin@catholic.ac.kr.|Catholic Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea. ckmin@catholic.ac.kr.
authors.forename: Chang-Ki
authors.initials: CK
authors.lastname: Min
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D010641:Phenotype; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide
keywords: Lenalidomide; Low-dose dexamethasone; Multiple myeloma; Myeloid-derived suppressor cells; Natural killer T-like cells