T-Cell Lymphocyte Kinetics As a Predictive Biomarker of Blinatumomab MRD Response in ALL-B Patients: A Single-Center Prospective Study

INTRODUCTION

Blinatumomab is a bi-specific antibody anti-CD3 and anti-CD19 that acts as a T-cell engager: by binding CD19+ lymphoblasts, blinatumomab recruits cytotoxic CD3+ T-lymphocytes to target them toward cancer cells. Currently, there is limited knowledge regarding the patient's immune system before and during therapy with blinatumomab in patients affected by acute lymphoblastic leukemia-B (ALL-B).

METHODS

This prospective study aimed to evaluate the trend of global lymphocyte kinetics, T-effector, effector memory, Treg, and interferon-gamma level (INFγ) measured baseline and after the blinatumomab cycle. We measured by flow-cytometry the levels of lymphocytes TCD4-effector (T4-eff), TCD8-effector (T8-eff), T4 IFNγ, T8 IFNγ, T-regulatory (T-reg) at baseline (T0) and after 1^st cycle (T1) of Blinatumomab to identify variables correlated to the response of the disease. The results were reported as the ratio between T1/T0 and compared according to response to blinatumomab (Wilcoxon paired test).

RESULTS

Data from nine patients (4 male and 5 female) with a median age of 34.9 (range 16-57) treated with blinatumomab in our center were analyzed before and after the first cycle of blinatumomab. Indication to blinatumomab was, respectively, relapse in 3, MRD in 5, and maintenance as part of an experimental protocol in 1 patient. ALL-B was, respectively, Ph'- and Ph'+ in 6 and in 3 patients. Blinatumomab was administrated as 1st line in 2, 2nd line in 5, and 3^rd line in 2 patients. None of the patients underwent lymphodepleting therapy (e.g., cyclophosphamide) before blinatumomab.

Response after 1^st cycle was complete remission (CR) without MRD in 4, CR with MRD in 2, refractory in 2, and persistence of CR/MRD-negative in 1 patient, respectively.

After a median follow-up of 15 months (range 2-36), six patients are alive (2 after HSCT) without MRD, and 3 patients died of disease progression.

The mean ratios T1/T0 measured were, respectively: 2.1 for T4-eff and 2.17 for T8-eff (with data available in 7 patients), 3.32 for T4 IFNγ and 2.51 for T8 IFNγ (with data available in 5 patients). By comparing the results according to disease-response (responders vs non-responders) the mean T1/T0 ratios were, respectively, 2.56 vs 1.51 for T4-eff (p = 0.008), 2.54 vs 1.67 for T8-eff (p = 0.016), 3.88 vs 1.09 for T4 IFNγ (p = 0.03), 2.89 vs 1.02 for T8 IFNγ (p = 0.03) (figure 1).

CONCLUSION

Preliminary results evidence plausible association between T lymphocyte kinetics, including Inf-gamma production, and achievement of MRD negativity following the first blinatumomab cycle. Further studies with a larger population are needed to predict treatment response.

No relevant conflicts of interest to declare.