P1675: SUTIMLIMAB PROVIDES SUSTAINED IMPROVEMENTS IN PATIENT-REPORTED OUTCOMES AND QUALITY OF LIFE IN PATIENTS WITH COLD AGGLUTININ DISEASE: OPEN-LABEL EXTENSION OF THE PHASE 3 CADENZA STUDY

Topic: 35. Quality of life and palliative care Background: Cold agglutinin disease (CAD) is a rare subtype of autoimmune hemolytic anemia that is mediated by the classical complement pathway, leading to chronic hemolysis, fatigue, and poor quality of life (QoL). Treatment with sutimlimab – a C1s complement inhibitor – rapidly halted hemolysis, increased hemoglobin levels, and improved fatigue in patients with CAD with no recent history of transfusion (≤1 during the previous 12 months; 0 during the last 6 months) in the randomized, double-blind, placebo-controlled Part A of the Phase 3 CADENZA trial (NCT03347422). Rapid improvements compared with placebo were also observed for patient-reported outcomes (PROs) up to 26 weeks. Aims: To report the long-term effect of sutimlimab treatment on PROs in patients with CAD from Part B, the open-label extension of CADENZA. Methods: All patients who completed Part A were eligible to receive biweekly doses of sutimlimab in Part B (6.5 g if <75 kg or 7.5 g if ≥75 kg body weight), continuing up to 1 year after the last patient finished Part A. PRO endpoints included: incidence of solicited symptomatic anemia (presence/absence of fatigue, weakness, shortness of breath, palpitations, light-headedness, and/or chest pain) and change in these symptoms by visit (improvement, unchanged, or worsened); Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score; 12-Item Short Form Health Survey (SF-12) physical and mental component score (PCS, MCS); EuroQol visual analog scale (EQ-VAS); Patient Global Impression of Change (PGIC), and Patient Global Impression of [fatigue] Severity (PGIS). Results: In total, 39 patients entered Part B, and 32 (82.1%) completed. At Part A baseline (BL), 31/39 (79.5%) patients reported at least one solicited symptom of anemia, which decreased to 10/28 (35.7%) in all patients at Week 87 (Figure 1A). The most reported symptoms of anemia were fatigue, weakness, and shortness of breath at both time points. Improvement in at least one solicited symptom of anemia versus BL was observed in 22/28 (78.6%) at Week 87. Improvements in FACIT-Fatigue from BL were seen throughout Part B, with the mean change exceeding the clinically important change (CIC) of 5 points at all Part B visits up to Week 87 (Figure 1B). Improvements in PCS and MCS component scores of the SF-12 versus BL were observed in Part B, with a mean (SE) change from BL at Week 87 of 7.20 (2.06) and 3.93 (1.92) points respectively (n=27 for both). For the PCS, improvements were sustained above the CIC of 3.9 points through 87 weeks. EQ-VAS showed a consistent increase from BL, with mean (SE) change from BL at Week 87 of 15.57 (4.01, n=28) points. PGIC remained positive throughout the treatment period, with 20/28 (71.4%) of patients still reporting improvement from BL at Week 87. PGIS improved from 14/30 (46.7%) patients reporting “none” or “mild” fatigue at BL to 22/28 (78.5%) at Week 87. Summary/Conclusion: Sustained benefits from sutimlimab treatment in CADENZA Part B were observed across several PRO measures for 1 year or more after initiation of sutimlimab. These findings demonstrate that continued inhibition of the classical complement pathway via treatment with sutimlimab results in meaningful long-term benefits to fatigue and patient-reported QoL, in addition to improving symptomatic anemia in patients with CAD. Figure:Keywords: Autoimmune hemolytic anemia (AIHA), Quality of life, Patient reported outcomes