Contributions
Abstract: P1260
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Background: Dimethyl fumarate (DMF) treatment causes lymphopenia in a fraction of patients with multiple sclerosis (MS), as also reported in phase III trials. Prolonged and severe lymphopenia may potentially increase the risk of opportunistic infections; nevertheless, recent data suggest that DMF-induced lymphopenia might be a biomarker for drug response.
Objective: To assess (1) the role of baseline demographic and clinical factors in DMF-induced lymphopenia and (2) whether early on-treatment absolute lymphocyte count (ALC) is related to short-term disease activity.
Methods: We included prospectively all patients starting DMF at the MS Centre of S. Camillo-Forlanini Hospital in Rome from 2014 to 2017. Baseline demographic and clinical factors associated with the risk of grade 3 lymphopenia (ALC< 500-200/mmc) were assessed by logistic regression analysis. A Cox regression analysis, adjusted by baseline demographic, clinical and laboratory variables, was run to test the association between ALC drop in the first 6 treatment months and the risk of subsequent relapses. Receiver-operating characteristic (ROC) analysis identified the optimal cut-off value of age predicting lymphopenia and of ALC drop predicting the relapse risk.
Results: A total of 181 patients (115 F, 66 M; 44 treatment-naives) with a mean age of 40±10 years, mean MS duration of 11±9 years and median baseline EDSS score of 1.5 started DMF. Data on ALC were available for 137 patients at year 1 and 85 patients at year 2. Seventeen (12%) patients developed grade 3 lymphopenia (10 during the first and 7 during the second treatment year). No grade 4 lymphopenia was found. We did not observe any lymphopenia-related adverse event. Older age was the only factor associated with an increased risk of lymphopenia (OR=1.08, p=0.01), with the “warning” age starting after 40 years. Twenty-five (18%) patients relapsed during the follow-up. We found an increased risk of relapse in patients who had a less pronounced ALC drop at month 6 (HR=1.96, p=0.02). An ALC drop≥25% at month 6 (compared to baseline) was the best cut-off value predicting a protective role on the relapse risk.
Discussion: In our cohort, grade 3 DMF-induced lymphopenia was more frequent than that reported in clinical trials (12% vs. 4-5%). However, our findings generate the hypothesis of a relationship between early ALC drop and risk of on-treatment relapses, suggesting an ALC drop cut-off value at month 6 potentially useful in clinical practice.
Disclosure: CT: advisory boards and/or travel grants and/or speaker honoraria from Merck Serono, Roche, Teva Italia, Biogen, Almirall, Novartis, Sanofi-Genzyme.
LP: consulting fees from Biogen, Novartis and Roche; speaker honoraria from Almirall, Biogen, Genzyme, Merck Serono, Novartis and Teva; travel grants from Biogen, Genzyme, Novartis and Teva; research grants from the Italian MS Society (Associazione Italiana Sclerosi Multipla) and Genzyme.
SR: speaking honoraria from Teva, Merck Serono, Biogen; travel grant from Biogen, Merck Serono; advisory board consultant from Merck Serono and Novartis.
SH: consulting fees, speaker honoraria and travel grants from Biogen, Genzyme, Teva, CSL Behrig, Zambon; research grants from Italian Minister of Foreign Affairs.
SG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Almirall, Sanofi-Aventis, Novartis, Genzyme.
CG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Sanofi, Novartis, Genzyme.
Abstract: P1260
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Background: Dimethyl fumarate (DMF) treatment causes lymphopenia in a fraction of patients with multiple sclerosis (MS), as also reported in phase III trials. Prolonged and severe lymphopenia may potentially increase the risk of opportunistic infections; nevertheless, recent data suggest that DMF-induced lymphopenia might be a biomarker for drug response.
Objective: To assess (1) the role of baseline demographic and clinical factors in DMF-induced lymphopenia and (2) whether early on-treatment absolute lymphocyte count (ALC) is related to short-term disease activity.
Methods: We included prospectively all patients starting DMF at the MS Centre of S. Camillo-Forlanini Hospital in Rome from 2014 to 2017. Baseline demographic and clinical factors associated with the risk of grade 3 lymphopenia (ALC< 500-200/mmc) were assessed by logistic regression analysis. A Cox regression analysis, adjusted by baseline demographic, clinical and laboratory variables, was run to test the association between ALC drop in the first 6 treatment months and the risk of subsequent relapses. Receiver-operating characteristic (ROC) analysis identified the optimal cut-off value of age predicting lymphopenia and of ALC drop predicting the relapse risk.
Results: A total of 181 patients (115 F, 66 M; 44 treatment-naives) with a mean age of 40±10 years, mean MS duration of 11±9 years and median baseline EDSS score of 1.5 started DMF. Data on ALC were available for 137 patients at year 1 and 85 patients at year 2. Seventeen (12%) patients developed grade 3 lymphopenia (10 during the first and 7 during the second treatment year). No grade 4 lymphopenia was found. We did not observe any lymphopenia-related adverse event. Older age was the only factor associated with an increased risk of lymphopenia (OR=1.08, p=0.01), with the “warning” age starting after 40 years. Twenty-five (18%) patients relapsed during the follow-up. We found an increased risk of relapse in patients who had a less pronounced ALC drop at month 6 (HR=1.96, p=0.02). An ALC drop≥25% at month 6 (compared to baseline) was the best cut-off value predicting a protective role on the relapse risk.
Discussion: In our cohort, grade 3 DMF-induced lymphopenia was more frequent than that reported in clinical trials (12% vs. 4-5%). However, our findings generate the hypothesis of a relationship between early ALC drop and risk of on-treatment relapses, suggesting an ALC drop cut-off value at month 6 potentially useful in clinical practice.
Disclosure: CT: advisory boards and/or travel grants and/or speaker honoraria from Merck Serono, Roche, Teva Italia, Biogen, Almirall, Novartis, Sanofi-Genzyme.
LP: consulting fees from Biogen, Novartis and Roche; speaker honoraria from Almirall, Biogen, Genzyme, Merck Serono, Novartis and Teva; travel grants from Biogen, Genzyme, Novartis and Teva; research grants from the Italian MS Society (Associazione Italiana Sclerosi Multipla) and Genzyme.
SR: speaking honoraria from Teva, Merck Serono, Biogen; travel grant from Biogen, Merck Serono; advisory board consultant from Merck Serono and Novartis.
SH: consulting fees, speaker honoraria and travel grants from Biogen, Genzyme, Teva, CSL Behrig, Zambon; research grants from Italian Minister of Foreign Affairs.
SG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Almirall, Sanofi-Aventis, Novartis, Genzyme.
CG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Sanofi, Novartis, Genzyme.