Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia

• Published in: Blood Vol. 145; no. 4; pp. 397 - 408
• Main Authors: Roman, Eloy, Fattizzo, Bruno, Shum, Merrill, Hanna, Wahid, Lentz, Steven R., Araujo, Sergio Schusterschitz S., Al-Adhami, Mohammed, Grossi, Federico V., Gertz, Morie A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.01.2025
• Subjects: Adult; Aged; Anemia, Hemolytic, Autoimmune - blood; Anemia, Hemolytic, Autoimmune - drug therapy; Anemia, Hemolytic, Autoimmune - immunology; Female; Humans; Male; Middle Aged; Treatment Outcome
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2023022549

•Pegcetacoplan treatment increased Hb levels, reduced hemolysis, and increased FACIT-fatigue scale scores in patients with CAD and wAIHA. [Display omitted] Cold agglutinin disease (CAD) and warm antibody autoimmune hemolytic anemia (wAIHA) are rare autoimmune hemolytic anemias characterized by red blood cell destruction, largely attributable to complement activation resulting in intravascular and extravascular hemolysis. Pegcetacoplan is a subcutaneously administered C3-targeted therapy, which may be suitable for treating CAD and wAIHA. In this open-label phase 2 study, analyses were conducted in 2 cohorts, 1 for patients with CAD and the other for those with wAIHA. In each cohort, patients were randomly assigned to receive pegcetacoplan 270 mg/d or 360 mg/d for up to 48 weeks. Safety end points included the incidence and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI). Efficacy end points included change from baseline in hemoglobin (Hb), lactate dehydrogenase, absolute reticulocyte count, haptoglobin, indirect bilirubin, and functional assessment of chronic illness therapy (FACIT)-fatigue scale. Thirteen of 13 (100%) and 10 of 11 (91%) patients with CAD and wAIHA, respectively, experienced at least 1 TEAE. Ten patients had at least 1 serious AE; none were considered related to pegcetacoplan. The only treatment-related AESIs were injection site reactions. Pegcetacoplan increased Hb levels, reduced hemolysis, and increased FACIT-fatigue scale scores in the first weeks; at week 48 the median (interquartile range) change from baseline Hb for the CAD and wAIHA total groups was 2.4 (0.90-3.00) and 1.7 g/dL (−1.40 to 2.90), respectively, and improvements in hemolysis and FACIT-fatigue scale scores were maintained. This study demonstrated that pegcetacoplan is generally well tolerated and suggests it can be effective for patients with CAD and wAIHA. This trial was registered at www.ClinicalTrials.gov as #NCT03226678. Some antibodies that drive autoimmune hemolytic anemia do so by activating complement, including immunoglobulin M antibodies causing cold agglutinin disease (CAD) and some immunoglobulin G subclasses causing warm autoimmune hemolytic anemia (wAIHA). Roman and colleagues report the results of PLAUDIT, a phase 2 study of pegcetacoplan, a C3 complement inhibitor, in primary CAD and wAIHA. The authors found that by 8 weeks and over 48 weeks, hemolysis was reduced, hemoglobin levels increased, fatigue scores improved, and that the drug was well tolerated. Pegcetacoplan may represent an effective therapy for CAD in selected patients with wAIHA, and a phase 3 trial is ongoing.