D. Landi

UOSD Centro di Riferimento Regionale Sclerosi Multipla Dipartimento di Neuroscienze Policlinico Tor Vergata

Author Of 1 Presentation

Disease Modifying Therapies – Risk Management Oral Presentation

FC02.03 - Evaluation of T and B lymphocytopenia in patients treated with Ocrelizumab switching from other treatments compared to naive

Speakers
Presentation Number
FC02.03
Presentation Topic
Disease Modifying Therapies – Risk Management
Lecture Time
13:24 - 13:36

Abstract

Background

Ocrelizumab (Ocre) is an anti-CD20 monoclonal antibody with a known major depleting effect on B cells and marginal on T cells. It is approved for clinical use in highly-active naïve multiple sclerosis (MS) patients and those not responder to previous treatment. In MS patients switching from other drugs prolonged dysfunction of adaptive immune system may occur after discontinuation, posing the need to carefully investigate the safety profile of treatment sequencing.

Objectives

To investigate the B and T cells subsets longitudinal dynamic during treatment with Ocre in patients with MS switching from Fingolimod (FTY) and other treatments (Dimetylfumarate, Interferon Beta, Glatiramer Acetate, Natalizumab, Teriflunomide) compared to naïve patients.

Methods

A multicenter observational 2-year study was conducted in patients starting treatment with Ocre grouped in three arms: naïve (naïve), switching from FTY (pre-FTY), switching from other treatments (other). Data about lymphocyte subtype count (CD3+, CD4+, CD8+ and CD20+) were collected at baseline and every 6 months after starting Ocre. Slope of reduction and proportion of patients with lymphocytes count below the normal lower limit was calculated.

Results

A sample of 135 patients was analysed (37 pre-FTY, 64 other, 34 naïve). At baseline pre-FTY compared to naïve showed significant decrease of CD3+ (1204.54+675.37 cells/mm3 vs 1735.53+653.56, p=0.0003), CD4+ (551.91+254.42 vs 997.03+352.79, p<0.0001), CD8+ (430.38+379.73 vs 537.75+254.34, p=0.027) and CD20+ (88.25+90.94 vs 191.32+149.62, p=0.021) cells. During Ocre the slope of reduction of CD3+ in naïve patients was 5.45 cells/mm3/week (p=0.003). Compared to naïve, the rate of decrease in CD3+ was -1.2 cells/mm3/week in pre-FTY (p=0.087) and +0.19 (p=0.012) in other. The slope of reduction of CD4+ was 2.00 cells/mm3/week in naïve (p=0.072). Compared to naïve the rate of reduction in CD4+ was +0.91 cells/mm3/week in pre-FTY (p=0.061) and +1.70 cells/mm3/week (p=0.012) in other. CD8+ and CD20+ cells decrease was similar among groups (p for interaction between time and treatment = 0.184 and 0.108, respectively). In pre-FTY group compared to baseline the proportion of patients with CD3+ and CD4+ cells lymphopenia was unchanged (16.22% versus 17.14% ; 32.35% versus 34.29%), while the proportion of CD8+ cells was increased (8.82% versus 25.71%).

Conclusions

Our study confirms that Ocre may induce depletion of T cell subsets beyond B cells. Nevertheless, in pre-FTY we also observed a prolonged T- lymphocytopenia , as carry-over effect of the previous therapy. FTY-induced immunosenescence or slow immunoreconstitution may explain this finding.

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Presenter Of 1 Presentation

Disease Modifying Therapies – Risk Management Oral Presentation

FC02.03 - Evaluation of T and B lymphocytopenia in patients treated with Ocrelizumab switching from other treatments compared to naive

Speakers
Presentation Number
FC02.03
Presentation Topic
Disease Modifying Therapies – Risk Management
Lecture Time
13:24 - 13:36

Abstract

Background

Ocrelizumab (Ocre) is an anti-CD20 monoclonal antibody with a known major depleting effect on B cells and marginal on T cells. It is approved for clinical use in highly-active naïve multiple sclerosis (MS) patients and those not responder to previous treatment. In MS patients switching from other drugs prolonged dysfunction of adaptive immune system may occur after discontinuation, posing the need to carefully investigate the safety profile of treatment sequencing.

Objectives

To investigate the B and T cells subsets longitudinal dynamic during treatment with Ocre in patients with MS switching from Fingolimod (FTY) and other treatments (Dimetylfumarate, Interferon Beta, Glatiramer Acetate, Natalizumab, Teriflunomide) compared to naïve patients.

Methods

A multicenter observational 2-year study was conducted in patients starting treatment with Ocre grouped in three arms: naïve (naïve), switching from FTY (pre-FTY), switching from other treatments (other). Data about lymphocyte subtype count (CD3+, CD4+, CD8+ and CD20+) were collected at baseline and every 6 months after starting Ocre. Slope of reduction and proportion of patients with lymphocytes count below the normal lower limit was calculated.

Results

A sample of 135 patients was analysed (37 pre-FTY, 64 other, 34 naïve). At baseline pre-FTY compared to naïve showed significant decrease of CD3+ (1204.54+675.37 cells/mm3 vs 1735.53+653.56, p=0.0003), CD4+ (551.91+254.42 vs 997.03+352.79, p<0.0001), CD8+ (430.38+379.73 vs 537.75+254.34, p=0.027) and CD20+ (88.25+90.94 vs 191.32+149.62, p=0.021) cells. During Ocre the slope of reduction of CD3+ in naïve patients was 5.45 cells/mm3/week (p=0.003). Compared to naïve, the rate of decrease in CD3+ was -1.2 cells/mm3/week in pre-FTY (p=0.087) and +0.19 (p=0.012) in other. The slope of reduction of CD4+ was 2.00 cells/mm3/week in naïve (p=0.072). Compared to naïve the rate of reduction in CD4+ was +0.91 cells/mm3/week in pre-FTY (p=0.061) and +1.70 cells/mm3/week (p=0.012) in other. CD8+ and CD20+ cells decrease was similar among groups (p for interaction between time and treatment = 0.184 and 0.108, respectively). In pre-FTY group compared to baseline the proportion of patients with CD3+ and CD4+ cells lymphopenia was unchanged (16.22% versus 17.14% ; 32.35% versus 34.29%), while the proportion of CD8+ cells was increased (8.82% versus 25.71%).

Conclusions

Our study confirms that Ocre may induce depletion of T cell subsets beyond B cells. Nevertheless, in pre-FTY we also observed a prolonged T- lymphocytopenia , as carry-over effect of the previous therapy. FTY-induced immunosenescence or slow immunoreconstitution may explain this finding.

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