Individuals with cold agglutinin disease (CAD), a rare, chronic, autoimmune haemolytic anaemia, had sustained improvements in patient-reported outcomes (PROs) and quality of life (QoL) following treatment with the C1s complement inhibitor sutimlimab, findings from part B of the phase III CADENZA trial have shown.
“CAD symptoms, particularly fatigue, place a profound burden on patients, impacting their QoL. CAD is clearly not a benign disease. It is not unproblematic to most patients,” said study investigator Dr Alexander Röth from the University of Duisburg-Essen, Essen, Germany, at ASH 2022.
“In part B of CADENZA, PRO data demonstrated that the benefits associated with sutimlimab on fatigue and overall QoL were maintained for >1 year,” Röth continued.
CADENZA included 42 CAD patients without recent history of transfusion. Part A comprised a 26-week double-blind phase whereby participants received placebo or sutimlimab at weeks 0 and 1, and then every 2 weeks. In part B, 39 patients (mean age 67 years, 80 percent female) who completed part A received biweekly doses of sutimlimab 6.5 g (<75 kg) or 7.5 g (≥75 kg), running up to 1 year after the last patient has completed part A. [ASH 2022, abstract 31]
There were rapid and sustained improvements in FACIT-Fatigue* score with long-term sutimlimab use. On first evaluation of those who switched from placebo to sutimlimab, mean change in FACIT-Fatigue score was 8.0 points. On the last on-treatment visit (LV) of all patients, mean change was 8.8 points. Röth noted that these were clinically meaningful improvements as the scores “exceeded the clinically important change (CIC) of 5 points.”
At baseline, 47 percent of participants had improvement in PGIS** (no or mild fatigue). By week 87, more than three quarters (78 percent) have achieved this endpoint.
PGIC*** also remained positive throughout the treatment period, with 71 percent of all patients reporting improvement from baseline to week 87.
At LV, mean changes in SF-12 PCS and MCS# for all patients were 4.9 and 4.0 points, respectively. These surpassed the respective CICs of 3.9 and 2.8 points. There was also a consistent improvement in EQ VAS## (mean change 15.3 points).
Sustained haematologic response
Mean total bilirubin levels that have normalized with sutimlimab in part A was sustained up until LV in part B. “Similar decreases were observed for patients previously treated with placebo when they started receiving sutimlimab in part B,” Röth said. “In CAD, it is always important to look at bilirubin because it is the most immediate parameter which tells about haemolytic activity.”
As for haemoglobin levels, the improvement achieved by sutimlimab recipients in part A were sustained throughout the study. For those who switched, haemoglobin levels rapidly increased following the transition from placebo to sutimlimab, reaching levels comparable to those who have been receiving the drug from baseline.
Meaningful long-term benefits
The current findings support the part A results, which have demonstrated the ability of sutimlimab to rapidly halt haemolysis, increase
haemoglobin levels, and improve fatigue, PROs, and QoL in this patient setting. [Blood 2022;140:980-991; EHA 2021, abstract S290]
“[Taken together, the current results suggest 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 haematologic parameters in CAD patients without recent history of transfusion,” Röth concluded.