Journal Information
Vol. 42. Issue S2.
Pages 57-58 (November 2020)
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Vol. 42. Issue S2.
Pages 57-58 (November 2020)
Open Access
M.M.O. Barrosa, A. Röthb, W. Barcellinic, T.H.A. Tvedtd, Y. Miyakawae, D.J. Kuterf, W. Hobbsg, J. Suh, X. Jiangi, J.M. Ariash, I.C. Weitzi
a Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
b Department of Hematology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
c Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, Milan, Italy
d Section for Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
e Thrombosis and Hemostasis Center, Saitama Medical University Hospital, Saitama, Japan
f Division of Hematology, Massachusetts General Hospital, Harvard Medical School, Boston, United States
g Sanofi, Waltham, United States
h Sanofi, Cambridge, United States
i Jane Anne Nohl Division of Hematology, Department of Medicine, University of Southern California–Keck School of Medicine, Los Angeles, United States
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Aims: Describe the effect of sutimlimab on patient-reported outcomes (PRO) as a measure of quality of life (QoL), as assessed in Part A of the Phase 3 Cardinal study (NCT03347396). Methods: Cardinal is an open-label, single-arm study in patients with Cold agglutinin disease (CAD). Part A evaluated the efficacy and safety of sutimlimab over 26 weeks. Patients with primary CAD and ≥ 1 blood transfusion in the prior 6 months were enrolled. Informed consent was provided. Sutimlimab was administered intravenously on Days 0 and 7, and biweekly thereafter. Patients weighing<75kg or ≥ 75kg received a 6.5g or 7.5g dose, respectively. Mean change from baseline in fatigue was assessed as a secondary endpoint using the Therapy-Fatigue (FACIT-F) scale at the treatment assessment time point (TAT; defined as the average of the values from Weeks 23, 25, and 26). Mean change from baseline for exploratory endpoints of QoL was assessed using the 5-level EuroQol 5 dimensions questionnaire (EQ-5D-5L) and the 12-Item Short Form Health Survey (SF-12). Results were reported using descriptive statistics. Results: Patients with CAD in this study were characterized by abnormal baseline QoL measures consistent with conditions such as cancer and autoimmune disorders and demonstrated clinically meaningful improvements across all PROs measured after treatment with sutimlimab. Of 24 patients enrolled, 17 had evaluable FACIT-F values at the TAT. Improvements in FACIT-F score were observed by Week 1 and were maintained through Week 26. Mean (standard deviation [SD]) FACIT-F scores increased from 32.5 (10.6) at baseline (a score indicative of severe fatigue) to 44.3 (6.5) at the TAT, with an estimated mean (standard error) FACIT-F score increase of 10.9 (1.4). Clinically meaningful FACIT-F improvements (≥3-point increases) were achieved in ≥ 75% of patients (interquartile range: 5.0–15.5 points). Among the 16 patients evaluable for EQ-5D-5L, the mean (SD) increases in index and visual analog scale scores from baseline to Week 26 were 0.074 (0.185) and 16.8 (16.9), respectively. Mobility and usual activities domains had the greatest improvements. The mean (SD) increases in SF-12 physical and mental component scores from baseline to Week 26 were 5.37 (7.60) and 4.37 (10.02) points (n=16), respectively. Improvements in all these QoL measures correlated with resolution of hemolysis, near-complete inhibition of CP activity, and rapid normalization of complement C4. Conclusions: The Phase 3 Cardinal study demonstrated that, in addition to the degree of anemia, CP activation with subsequent hemolysis plays a critical role as a driver of fatigue symptoms and poor QoL in patients with CAD. Treatment with sutimlimab, an inhibitor of complement C1s, resulted in rapid, clinically meaningful improvements in all PRO measures evaluated, further supporting the effectiveness of targeting the CP in the management of patients with this condition. Data first presented at EHA 2020, 11th-21st June 2020.

Hematology, Transfusion and Cell Therapy

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