Contributions
Abstract: P935
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: The humanized anti-CD52 monoclonal antibody alemtuzumab is a highly effective disease-modifying treatment (DMT) for relapsing-remitting multiple sclerosis (RRMS). It is administered in two yearly courses of 12 mg/day during 5 days and 3 days respectively. It induces profound lymphopenia and the rate and degree of recovery varies with cell type. In clinical trials (CT), lymphocyte count recovery after alemtuzumab was followed in patients with injectable immunomodulators as previous DMT and in naive patients.
Objective: To investigate of the kinetics and relative recovery of CD4 and CD8 T cells, CD19 B, CD56 NK and CD45+ cells after alemtuzumab in patients previously undertaking Fingolimod.
Methods: A total of 32 patients with RRMS previously treated with Fingolimod underwent first course of alemtuzumab were followed. Peripheral blood mononuclear cell phenotyping (PBMCP) was performed at baseline and the quarterly. Last PBMCP was done just before of second course.
Results: Mean age of patients was 34.8±6.4 years and 59,3% were female. One year after first course, a profound depletion of all lymphocyte lines was observed excepting from CD19 lymphocytes, which showed a slight increase. Comparison among cell subsets counts between before the first course and prior to the second course was made. There was significant difference between CD3 (1054±665 vs 465±228 cells/mL, p= 0,005), CD4 (627±471 vs 189±88 cells/mL, p= 0,02) and CD45 (1681±997 vs 1028±365 cells/mL, p= 0,01). Non-significant difference was found between CD19 (199±247 vs 307±161 cells/mL, p=0,14), CD8 (392±235 vs 265±193 cells/mL, p=0,11) and CD56 NK (221±159 vs 206±134 cells/mL, p=0,68).12,5% of patients had less than 200 CD4+ cells/mL before the first course and 54,16% prior the second cycle (p< 0,005). This finding did not delay the second course.
Conclusion: Our data show a persistent depletion of CD4 count below 200 cells/mL in a high proportion of patients just before of second course, despite the fact that alemtuzumab is not known to have a significant effect on lymphocyte precursors. It may relate to an effect on CD52-expressing thymocytes, a disease-specific impairment of lymphocyte homeostasis in MS or DMT background. The influence of previous depletion of CD4 in long-term efficacy, tolerability and safety of alemtuzumab is currently unknown.
Disclosure: José María Cabrera Maqueda: Nothing to disclose
Luna Fuentes Rumí: Nothing to disclose
Ester Carreón Guarnizo: Nothing to disclose
Rocío Hernández Clares:Nothing to disclose
Julián Vázquez Lorenzo: Nothing to disclose
Ana Ester Baidez Guerrero Ana Ester: Nothing to disclose
Judith Jimenez Veiga: Nothing to disclose
Adelaida Leon Herna Marin: Nothing to disclose
Joaquín Zamarro Parra: Nothing to disclose
P. Velázquez Marín: Nothing to disclose
P. Iniesta Martinez: Nothing to disclose
Ana Morales Ortiz: Nothing to disclose
JE Meca Lallana: Nothing to disclose
Abstract: P935
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: The humanized anti-CD52 monoclonal antibody alemtuzumab is a highly effective disease-modifying treatment (DMT) for relapsing-remitting multiple sclerosis (RRMS). It is administered in two yearly courses of 12 mg/day during 5 days and 3 days respectively. It induces profound lymphopenia and the rate and degree of recovery varies with cell type. In clinical trials (CT), lymphocyte count recovery after alemtuzumab was followed in patients with injectable immunomodulators as previous DMT and in naive patients.
Objective: To investigate of the kinetics and relative recovery of CD4 and CD8 T cells, CD19 B, CD56 NK and CD45+ cells after alemtuzumab in patients previously undertaking Fingolimod.
Methods: A total of 32 patients with RRMS previously treated with Fingolimod underwent first course of alemtuzumab were followed. Peripheral blood mononuclear cell phenotyping (PBMCP) was performed at baseline and the quarterly. Last PBMCP was done just before of second course.
Results: Mean age of patients was 34.8±6.4 years and 59,3% were female. One year after first course, a profound depletion of all lymphocyte lines was observed excepting from CD19 lymphocytes, which showed a slight increase. Comparison among cell subsets counts between before the first course and prior to the second course was made. There was significant difference between CD3 (1054±665 vs 465±228 cells/mL, p= 0,005), CD4 (627±471 vs 189±88 cells/mL, p= 0,02) and CD45 (1681±997 vs 1028±365 cells/mL, p= 0,01). Non-significant difference was found between CD19 (199±247 vs 307±161 cells/mL, p=0,14), CD8 (392±235 vs 265±193 cells/mL, p=0,11) and CD56 NK (221±159 vs 206±134 cells/mL, p=0,68).12,5% of patients had less than 200 CD4+ cells/mL before the first course and 54,16% prior the second cycle (p< 0,005). This finding did not delay the second course.
Conclusion: Our data show a persistent depletion of CD4 count below 200 cells/mL in a high proportion of patients just before of second course, despite the fact that alemtuzumab is not known to have a significant effect on lymphocyte precursors. It may relate to an effect on CD52-expressing thymocytes, a disease-specific impairment of lymphocyte homeostasis in MS or DMT background. The influence of previous depletion of CD4 in long-term efficacy, tolerability and safety of alemtuzumab is currently unknown.
Disclosure: José María Cabrera Maqueda: Nothing to disclose
Luna Fuentes Rumí: Nothing to disclose
Ester Carreón Guarnizo: Nothing to disclose
Rocío Hernández Clares:Nothing to disclose
Julián Vázquez Lorenzo: Nothing to disclose
Ana Ester Baidez Guerrero Ana Ester: Nothing to disclose
Judith Jimenez Veiga: Nothing to disclose
Adelaida Leon Herna Marin: Nothing to disclose
Joaquín Zamarro Parra: Nothing to disclose
P. Velázquez Marín: Nothing to disclose
P. Iniesta Martinez: Nothing to disclose
Ana Morales Ortiz: Nothing to disclose
JE Meca Lallana: Nothing to disclose