NK and T-lymphocyte Kinetics Predict Outcome in Myeloma Patients Treated With Elotuzumab, Lenalidomide Plus Dexamethasone.

Abstract

Elotuzumab, an anti-SLAMF7 monoclonal antibody, can enhance immune activity via elevated antibody-dependent cellular cytotoxicity and reduced SLAMF7+CD8+CD57+ regulatory T-cells (Tregs). This multicenter observational study investigated the kinetics of lymphocytes in myeloma patients treated with elotuzumab, lenalidomide, and dexamethasone (ERd) by two-color flow cytometry using peripheral blood samples. Twenty-one patients were included in this study. The median duration of ERd was 22.6 months, and the cutoff time for long-duration ERd was two years. The CD2+CD16+ and CD16+CD57- NK cells were significantly increased over time in the long-duration ERd group compared to those in the short-duration ERd group (p=0.035 and p<0.001). The CD8+ and CD16-CD57+ lymphocytes, identified as low-activity NK cells or SLAMF7+ Tregs, were significantly increased in the patients whose ERd outcome was progressive disease (PD) compared to those in the non-PD group (p=0.023 and p<0.001). The mean CD4/CD8 ratio and CD19+ lymphocyte counts in the long-duration ERd group were significantly lower than those in the short-duration ERd group, although the kinetics of them did not change over time (p=0.016 and p=0.011). When the cutoff value of CD4/CD8 ratio was 0.792 according to ROC curves, the two-year time to next treatment (TTNT) in the low CD4/CD8 group was significantly longer than that in the high CD4/CD8 group (80.0% vs. 15.0%, p=0.024). The change in NK cells and CD8+ Tregs predicted long-duration ERd and PD, and maintaining low CD4/8 ratio predicted long TTNT, suggesting that these lymphocyte fractions might be biomarkers for a durable therapeutic effect of ERd in myeloma patients.