Contributions
Abstract: P1250
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Alemtuzumab-induced lymphocyte depletion is associated with cytokine-release syndrome during the drug administration (explaining the frequent infusion associated reaction, IARs) and with increased infection risk in the following months. Despite the pharmacological and dietary strategies applied, these events are still frequent and potentially harmful.
Objective: To investigate the clinical or laboratory variables associated with cytokine-release syndrome and infections, in order to identify MS patients at higher risk of developing severe and early adverse events (AEs).
Methods: Fifty-three MS patients (ratio female/ male: 2.1) treated with alemtuzumab between March 2015 and October 2017 at the MS Centres of Padua and Vicenza, were enrolled in this 6-month longitudinal study. Patients were carefully assessed for AEs (classified according to CTCAE v5) during the 5-day drug infusion and then monthly. Blood cell count and differentiation were acquired at baseline and after 3, 21, and 42 days (D3, D21, D42 respectively).
Results: At baseline, patients had mean age of 31.4±8.7 years, disease duration of 7.8±6.5 years, annualized-relapse rate of 1.2 (range 0-4) and mean number of previous treatment of 2.0 (0-6; twelve patients were treatment naïve). During drug infusion, related-AEs were observed in 85% of the patients: 30 (56.7%) patients had mild symptoms and 15 (28.3%) moderate, while no severe AE was observed. A significant association was found between the number of previous disease-modifying treatments and AE severity (r:0.361, p=0.008). AEs were significantly less frequent (58.3% vs 92.7%, p< 0.01) and shorter (1.1±1.2 vs 2.1±1.2 days, p< 0.01) in naïve than in previously treated patients. Within the first 60 days after drug infusion, 15 patients (28%) presented infections that in 5 cases required hospitalization (pneumoniae: 3; neutropenia with fever: 2). Multiple regression analysis showed that the risk of infection was associated with lower leukocyte count at D3 (β: 0.822, p< 0.05) and patient age (β: 1.1, p< 0.05). Cox survival analysis confirmed a higher rate of infection in patients with a leukocyte count at D3 below 11.96x109/L (O.R. 3.7, IC95% 1.3-10.7, p< 0.05).
Conclusion: As expected, alemtuzumab IARs were common, but never severe, and their risk decreased in treatment-naïve patients. All together, our findings indicate that the youngest and naïve patients have the lowest probability of alemtuzumab short-term AEs.
Disclosure: Puthenparampil Marco received travel grant from Novartis, Almirall, Genzyme, Biogen Idec, Teva and Sanofi Aventis; he has been consultant for Genzyme and Biogen Idec. Federle Lisa reports grants and personal fees from Novartis, grants and personal fees from Genzyme Sanofi, grants and personal fees from Biogen Italia, grants and personal fees from Almirall, grants and personal fees from Teva, grants and personal fees from Merck Serono, outside the submitted work. Gianola Stenta and Perini Francesco have nothing to disclose. Perini Paola has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, and Bayer Schering Pharma and has been consultant for Merck Serono, Biogen Idec and Teva. Rinaldi Francesca serves as an advisory board member of Biogen-Idec and has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, Teva and Bayer Schering Pharma. Gallo Paolo has been a consultant for Bayer Schering, Biogen Idec, Genzyme, Merck Serono and Novartis; has received funding for travel and speaker honoraria from Merck-Serono, Biogen Idec, Sanofi-Aventis, Novartis Pharma and Bayer-Schering Pharma, Teva; has received research support from Bayer, Biogen Idec/Elan, MerkSerono, Genzyme and Teva; and has received research grant from the University of Padova, Veneto Region of Italy, the Italian Association for Multiple Sclerosis, the Italian Ministry of Public Health.
Abstract: P1250
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Alemtuzumab-induced lymphocyte depletion is associated with cytokine-release syndrome during the drug administration (explaining the frequent infusion associated reaction, IARs) and with increased infection risk in the following months. Despite the pharmacological and dietary strategies applied, these events are still frequent and potentially harmful.
Objective: To investigate the clinical or laboratory variables associated with cytokine-release syndrome and infections, in order to identify MS patients at higher risk of developing severe and early adverse events (AEs).
Methods: Fifty-three MS patients (ratio female/ male: 2.1) treated with alemtuzumab between March 2015 and October 2017 at the MS Centres of Padua and Vicenza, were enrolled in this 6-month longitudinal study. Patients were carefully assessed for AEs (classified according to CTCAE v5) during the 5-day drug infusion and then monthly. Blood cell count and differentiation were acquired at baseline and after 3, 21, and 42 days (D3, D21, D42 respectively).
Results: At baseline, patients had mean age of 31.4±8.7 years, disease duration of 7.8±6.5 years, annualized-relapse rate of 1.2 (range 0-4) and mean number of previous treatment of 2.0 (0-6; twelve patients were treatment naïve). During drug infusion, related-AEs were observed in 85% of the patients: 30 (56.7%) patients had mild symptoms and 15 (28.3%) moderate, while no severe AE was observed. A significant association was found between the number of previous disease-modifying treatments and AE severity (r:0.361, p=0.008). AEs were significantly less frequent (58.3% vs 92.7%, p< 0.01) and shorter (1.1±1.2 vs 2.1±1.2 days, p< 0.01) in naïve than in previously treated patients. Within the first 60 days after drug infusion, 15 patients (28%) presented infections that in 5 cases required hospitalization (pneumoniae: 3; neutropenia with fever: 2). Multiple regression analysis showed that the risk of infection was associated with lower leukocyte count at D3 (β: 0.822, p< 0.05) and patient age (β: 1.1, p< 0.05). Cox survival analysis confirmed a higher rate of infection in patients with a leukocyte count at D3 below 11.96x109/L (O.R. 3.7, IC95% 1.3-10.7, p< 0.05).
Conclusion: As expected, alemtuzumab IARs were common, but never severe, and their risk decreased in treatment-naïve patients. All together, our findings indicate that the youngest and naïve patients have the lowest probability of alemtuzumab short-term AEs.
Disclosure: Puthenparampil Marco received travel grant from Novartis, Almirall, Genzyme, Biogen Idec, Teva and Sanofi Aventis; he has been consultant for Genzyme and Biogen Idec. Federle Lisa reports grants and personal fees from Novartis, grants and personal fees from Genzyme Sanofi, grants and personal fees from Biogen Italia, grants and personal fees from Almirall, grants and personal fees from Teva, grants and personal fees from Merck Serono, outside the submitted work. Gianola Stenta and Perini Francesco have nothing to disclose. Perini Paola has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, and Bayer Schering Pharma and has been consultant for Merck Serono, Biogen Idec and Teva. Rinaldi Francesca serves as an advisory board member of Biogen-Idec and has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, Teva and Bayer Schering Pharma. Gallo Paolo has been a consultant for Bayer Schering, Biogen Idec, Genzyme, Merck Serono and Novartis; has received funding for travel and speaker honoraria from Merck-Serono, Biogen Idec, Sanofi-Aventis, Novartis Pharma and Bayer-Schering Pharma, Teva; has received research support from Bayer, Biogen Idec/Elan, MerkSerono, Genzyme and Teva; and has received research grant from the University of Padova, Veneto Region of Italy, the Italian Association for Multiple Sclerosis, the Italian Ministry of Public Health.