Low Frequency of CD161+CD4+ T Cells Correlate with the Occurrence of Infections in Refractory/Relapsed Multiple Myeloma Patients Receiving Lenalidomide Plus Low-Dose Dexamethasone Treatment
Authors: Lee Sung-Eun , Lim Ji-Young , Ryu Da-Bin , Kim Tae Woo , Park Sung Soo , Jeon Young-Woo , Yoon Jae-Ho , Cho Byung-Sik , Eom Ki-Seong , Kim Yoo-Jin , Kim Hee-Je , Lee Seok , Cho Seok-Goo , Kim Dong-Wook , Lee Jong Wook , Min Woo-Sung , Min Chang-Ki 
Published: October 2019

Abstract
Background Although the combination of lenalidomide and low-dose dexamethasone (Len-dex) is known to preserve the efficacy with reduced toxicity than lenalidomide plus high-dose dexamethasone (Len-Dex) in patients with refractory/relapsed multiple myeloma (RRMM), infection is still a leading toxicity. Moreover, the patterns and risks for infection in patients with RRMM during Len-dex treatment remain unclear and there is a need to identify contributing factors associated with increased risk for infection. Considering the disease-related and treatment-related immune deficits in patients with RRMM, we explored the predictive implications of the revelation of the immune cell populations prior to Len-dex initiation for the occurrence of infection. In addition, the various clinical and laboratory parameters were analyzed.
Methods Clinical and microbiology records of 90 RRMM patients during Len-dex treatment were reviewed and risk factors for infection were analyzed using the logistic regression. In addition, to develop the new immune cell biomarker, we prospectively examined immune cell populations (CD3, CD4CD161, CD8CD161, Lin-HLA-DR-CD11b+CD33+, CD14+HLA-DR-, NK and NKT cells) of the peripheral blood taken on baseline of Len-dex therapy.
Results Forty-eight men and 42 women were enrolled in this study. The median age was 61 years (range, 29-84 years). During a median 11 cycles of Len-dex treatment, 52 (57.8%) patients experienced at least 1 infection episode. Of a total of 92 episodes of infection, 58 (63%) episodes were clinically defined, 29 (31.5%) episodes were microbiologically defined, and 5 (5.4%) episodes were fever of unknown focus. Severe episodes were frequently observed during early 3 cycles. In the univariate analyses, lower Hb (<10 g/dL) and serum albumin (<3.5 mg/dL), and higher serum creatinine (≥2 mg/dL) were associated with increased risk of infections (≥grade 3) during early 3 cycles. After adjusting for risk factors for infection on univariate analyses, multivariate analyses showed that lower Hb (<10 g/dL) was an independent factor for the occurrence of infections and lower frequency (P = 0.009) and absolute count (P = 0.072) of CD4+CD161+ cells in peripheral blood prior to Len-dex were associated with the occurrence of infection, especially during early 3 cycles of Len-dex therapy.
Conclusions We demonstrated several clinical predictive factors for the occurrence of infection in patients with RRMM receiving Len-dex treatment. And we found that the frequency and absolute count of CD4+CD161+ cells may provide additional information for predicting the occurrence of infection in early period of Len/dex therapy.

Disclosures
No relevant conflicts of interest to declare.