Author:
Casneuf Tineke,Adams Homer C.,van de Donk Niels W.C.J.,Abraham Yann,Bald Jaime,Vanhoof Greet,Van der Borght Koen,Smets Tina,Foulk Brad,Nielsen Karl C.,Rusbuldt Joshua,Axel Amy,Lysaght Andrew,Ceulemans Hugo,Stevenaert Frederik,Usmani Saad Z.,Plesner Torben,Avet-Loiseau Herve,Nijhof Inger,Mutis Tuna,Schecter Jordan M.,Chiu Christopher,Bahlis Nizar J.
Abstract
AbstractCD38-targeted antibody, daratumumab, is approved for the treatment of multiple myeloma (MM). Phase 1/2 studies GEN501/SIRIUS revealed a novel immunomodulatory mechanism of action (MOA) of daratumumab that enhanced the immune response, reducing natural killer (NK) cells without affecting efficacy or safety. We further evaluated daratumumab’s effects on immune cells in whole blood samples of relapsed/refractory MM patients from both treatment arms of the phase 3 POLLUX study (lenalidomide/dexamethasone [Rd] or daratumumab plus Rd [D-Rd]) at baseline (D-Rd, 40; Rd, 45) and after 2 months on treatment (D-Rd, 31; Rd, 33) using cytometry by time-of-flight. We confirmed previous reports of NK cell reduction with D-Rd. Persisting NK cells were phenotypically distinct, with increased expression of HLA-DR, CD69, CD127, and CD27. The proportion of T cells increased preferentially in deep responders to D-Rd, with a higher proportion of CD8+ versus CD4+ T cells. The expansion of CD8+ T cells correlated with clonality, indicating generation of adaptive immune response with D-Rd. D-Rd resulted in a higher proportion of effector memory T cells versus Rd. D-Rd reduced immunosuppressive CD38+ regulatory T cells. This study confirms daratumumab’s immunomodulatory MOA in combination with immunomodulatory drugs and provides further insight into immune cell changes and activation status following daratumumab-based therapy.
Funder
Janssen Global Services, LLC
Publisher
Springer Science and Business Media LLC
Subject
Oncology,Cancer Research,Hematology
Cited by
66 articles.
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