COMBINED BLINATUMOMAB + DASATINIB/IBRUTINIB THERAPY OF RELAPSED ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS – ANTILEUKEMIC EFFECT ON THE T-HELPER AND T-REGULATORY CELLS REDUCTION BACKGROUND.
(Abstract release date: 05/19/16)
EHA Library. Sokolov A. 06/09/16; 132416; E867
Dr. Andrey Sokolov
Contributions
Contributions
Abstract
Abstract: E867
Type: Eposter Presentation
Background
Blinatumomab, bispecific anti-CD3/CD19 monoclonal antibody, is effective as monotherapy in the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R-ALL), but long term results could be improved. T-regulatory (T-reg) and T-helper cells can inhibit effector T-cells used by blinatumomab. Tyrosine-kinase inhibitors (TKI) could be used in the treatment of both Ph-positive (Ph+) and Ph-negative (Ph-) ALL as pre-B-cell receptor signaling inhibitors.
Aims
To study T-cell subpopulations kinetics in R/R-ALL patients during combined blinatumomab + TKI treatment of relapsed ALL patients.
Methods
Two relapsed ALL patients (1 bone marrow Ph+ relapseand 1 extramedullary extraperitoneal with severe abdominal pain Ph- relapse)were treated with blinatumomab 28 mcg/day by continuous infusion 4 weeks cycles with 2 weeks intervals (3 cycles in Ph+ relapse and 2 cycles in Ph- patients). Dasatinib 140 mg/day started In Ph+ patient from the 3rd week of the first blinatumomab cycle and further continuously. Ibrutinib 560 mg/day started in Ph- patient from the 4th week of the first blinatumomab. T-cell subpopulations of the peripheral blood (T-helper, cytotoxic, T-reg, NK) were studied by flow cytometry every week during the whole treatment period. Blinatumomab was provided by Amgen sponsored Expanded Access Program.
Results
The Ph+ ALL patient treated by blinatumomab + dasatinib combination had pleural effusions and nonspecific lung infiltration fully regressed after 2 weeks dasatinib interruption. In that patient the second molecular remission was obtained after the second blinatumomab cycle + dasatinib treatment. In Ph- ALL patient the abdominal pain fully regressed and tumor size slightly decreased after the first blinatumomab cycle + ibrutinib. T-cell subpopulations study revealed only T-helper (lowered from 0,437 to 0,111x10*9/L in Ph+ ALL pt and was decreased to 0,112 – 0,111x10*9/L in Ph- ALL pt) and T-reg cell (was decreased to 0,006 – 0,002x10*9/L in Ph+ pt and lowered from 0,009 to 0,006x10*9/L in Ph- ALL pt) pools reduction. Absolute counts of cytotoxic T cells and NK cells remained within the normal reference values in both patients.
Conclusion
The correlation of the efficacy of blinatumomab treatment that uses effector cells in antileukemic effect against relapsed ALL with T-helper and T-reg pools reduction possibly indicates an overcoming the negative influence of those T-cell subpopulations. TKIs may act in synergy with blinatumomab during their concomitant use.
Session topic: E-poster
Keyword(s): Relapsed acute lymphoblastic leukemia, T lymphocyte, helper, T regulatory cells, Tyrosine kinase inhibitor
Type: Eposter Presentation
Background
Blinatumomab, bispecific anti-CD3/CD19 monoclonal antibody, is effective as monotherapy in the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R-ALL), but long term results could be improved. T-regulatory (T-reg) and T-helper cells can inhibit effector T-cells used by blinatumomab. Tyrosine-kinase inhibitors (TKI) could be used in the treatment of both Ph-positive (Ph+) and Ph-negative (Ph-) ALL as pre-B-cell receptor signaling inhibitors.
Aims
To study T-cell subpopulations kinetics in R/R-ALL patients during combined blinatumomab + TKI treatment of relapsed ALL patients.
Methods
Two relapsed ALL patients (1 bone marrow Ph+ relapseand 1 extramedullary extraperitoneal with severe abdominal pain Ph- relapse)were treated with blinatumomab 28 mcg/day by continuous infusion 4 weeks cycles with 2 weeks intervals (3 cycles in Ph+ relapse and 2 cycles in Ph- patients). Dasatinib 140 mg/day started In Ph+ patient from the 3rd week of the first blinatumomab cycle and further continuously. Ibrutinib 560 mg/day started in Ph- patient from the 4th week of the first blinatumomab. T-cell subpopulations of the peripheral blood (T-helper, cytotoxic, T-reg, NK) were studied by flow cytometry every week during the whole treatment period. Blinatumomab was provided by Amgen sponsored Expanded Access Program.
Results
The Ph+ ALL patient treated by blinatumomab + dasatinib combination had pleural effusions and nonspecific lung infiltration fully regressed after 2 weeks dasatinib interruption. In that patient the second molecular remission was obtained after the second blinatumomab cycle + dasatinib treatment. In Ph- ALL patient the abdominal pain fully regressed and tumor size slightly decreased after the first blinatumomab cycle + ibrutinib. T-cell subpopulations study revealed only T-helper (lowered from 0,437 to 0,111x10*9/L in Ph+ ALL pt and was decreased to 0,112 – 0,111x10*9/L in Ph- ALL pt) and T-reg cell (was decreased to 0,006 – 0,002x10*9/L in Ph+ pt and lowered from 0,009 to 0,006x10*9/L in Ph- ALL pt) pools reduction. Absolute counts of cytotoxic T cells and NK cells remained within the normal reference values in both patients.
Conclusion
The correlation of the efficacy of blinatumomab treatment that uses effector cells in antileukemic effect against relapsed ALL with T-helper and T-reg pools reduction possibly indicates an overcoming the negative influence of those T-cell subpopulations. TKIs may act in synergy with blinatumomab during their concomitant use.
Session topic: E-poster
Keyword(s): Relapsed acute lymphoblastic leukemia, T lymphocyte, helper, T regulatory cells, Tyrosine kinase inhibitor
Abstract: E867
Type: Eposter Presentation
Background
Blinatumomab, bispecific anti-CD3/CD19 monoclonal antibody, is effective as monotherapy in the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R-ALL), but long term results could be improved. T-regulatory (T-reg) and T-helper cells can inhibit effector T-cells used by blinatumomab. Tyrosine-kinase inhibitors (TKI) could be used in the treatment of both Ph-positive (Ph+) and Ph-negative (Ph-) ALL as pre-B-cell receptor signaling inhibitors.
Aims
To study T-cell subpopulations kinetics in R/R-ALL patients during combined blinatumomab + TKI treatment of relapsed ALL patients.
Methods
Two relapsed ALL patients (1 bone marrow Ph+ relapseand 1 extramedullary extraperitoneal with severe abdominal pain Ph- relapse)were treated with blinatumomab 28 mcg/day by continuous infusion 4 weeks cycles with 2 weeks intervals (3 cycles in Ph+ relapse and 2 cycles in Ph- patients). Dasatinib 140 mg/day started In Ph+ patient from the 3rd week of the first blinatumomab cycle and further continuously. Ibrutinib 560 mg/day started in Ph- patient from the 4th week of the first blinatumomab. T-cell subpopulations of the peripheral blood (T-helper, cytotoxic, T-reg, NK) were studied by flow cytometry every week during the whole treatment period. Blinatumomab was provided by Amgen sponsored Expanded Access Program.
Results
The Ph+ ALL patient treated by blinatumomab + dasatinib combination had pleural effusions and nonspecific lung infiltration fully regressed after 2 weeks dasatinib interruption. In that patient the second molecular remission was obtained after the second blinatumomab cycle + dasatinib treatment. In Ph- ALL patient the abdominal pain fully regressed and tumor size slightly decreased after the first blinatumomab cycle + ibrutinib. T-cell subpopulations study revealed only T-helper (lowered from 0,437 to 0,111x10*9/L in Ph+ ALL pt and was decreased to 0,112 – 0,111x10*9/L in Ph- ALL pt) and T-reg cell (was decreased to 0,006 – 0,002x10*9/L in Ph+ pt and lowered from 0,009 to 0,006x10*9/L in Ph- ALL pt) pools reduction. Absolute counts of cytotoxic T cells and NK cells remained within the normal reference values in both patients.
Conclusion
The correlation of the efficacy of blinatumomab treatment that uses effector cells in antileukemic effect against relapsed ALL with T-helper and T-reg pools reduction possibly indicates an overcoming the negative influence of those T-cell subpopulations. TKIs may act in synergy with blinatumomab during their concomitant use.
Session topic: E-poster
Keyword(s): Relapsed acute lymphoblastic leukemia, T lymphocyte, helper, T regulatory cells, Tyrosine kinase inhibitor
Type: Eposter Presentation
Background
Blinatumomab, bispecific anti-CD3/CD19 monoclonal antibody, is effective as monotherapy in the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R-ALL), but long term results could be improved. T-regulatory (T-reg) and T-helper cells can inhibit effector T-cells used by blinatumomab. Tyrosine-kinase inhibitors (TKI) could be used in the treatment of both Ph-positive (Ph+) and Ph-negative (Ph-) ALL as pre-B-cell receptor signaling inhibitors.
Aims
To study T-cell subpopulations kinetics in R/R-ALL patients during combined blinatumomab + TKI treatment of relapsed ALL patients.
Methods
Two relapsed ALL patients (1 bone marrow Ph+ relapseand 1 extramedullary extraperitoneal with severe abdominal pain Ph- relapse)were treated with blinatumomab 28 mcg/day by continuous infusion 4 weeks cycles with 2 weeks intervals (3 cycles in Ph+ relapse and 2 cycles in Ph- patients). Dasatinib 140 mg/day started In Ph+ patient from the 3rd week of the first blinatumomab cycle and further continuously. Ibrutinib 560 mg/day started in Ph- patient from the 4th week of the first blinatumomab. T-cell subpopulations of the peripheral blood (T-helper, cytotoxic, T-reg, NK) were studied by flow cytometry every week during the whole treatment period. Blinatumomab was provided by Amgen sponsored Expanded Access Program.
Results
The Ph+ ALL patient treated by blinatumomab + dasatinib combination had pleural effusions and nonspecific lung infiltration fully regressed after 2 weeks dasatinib interruption. In that patient the second molecular remission was obtained after the second blinatumomab cycle + dasatinib treatment. In Ph- ALL patient the abdominal pain fully regressed and tumor size slightly decreased after the first blinatumomab cycle + ibrutinib. T-cell subpopulations study revealed only T-helper (lowered from 0,437 to 0,111x10*9/L in Ph+ ALL pt and was decreased to 0,112 – 0,111x10*9/L in Ph- ALL pt) and T-reg cell (was decreased to 0,006 – 0,002x10*9/L in Ph+ pt and lowered from 0,009 to 0,006x10*9/L in Ph- ALL pt) pools reduction. Absolute counts of cytotoxic T cells and NK cells remained within the normal reference values in both patients.
Conclusion
The correlation of the efficacy of blinatumomab treatment that uses effector cells in antileukemic effect against relapsed ALL with T-helper and T-reg pools reduction possibly indicates an overcoming the negative influence of those T-cell subpopulations. TKIs may act in synergy with blinatumomab during their concomitant use.
Session topic: E-poster
Keyword(s): Relapsed acute lymphoblastic leukemia, T lymphocyte, helper, T regulatory cells, Tyrosine kinase inhibitor
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