Sutimlimab, an investigational C1s inhibitor, effectively prevents exacerbation of hemolytic anemia in a patient with cold agglutinin disease undergoing major surgery

@article{Tvedt2021SutimlimabAI,
  title={Sutimlimab, an investigational C1s inhibitor, effectively prevents exacerbation of hemolytic anemia in a patient with cold agglutinin disease undergoing major surgery},
  author={Tor Henrik A Tvedt and Egil Steien and Bente {\O}vreb{\o} and Rune Haaverstad and William Hobbs and Marek Wardęcki and Geir Erland Tj{\o}nnfjord and Sigbj{\o}rn Berentsen},
  journal={American Journal of Hematology},
  year={2021},
  volume={97}
}
1. Cory S, Roberts AW, Colman PM, Adams JM. Targeting BCL-2-like proteins to kill cancer cells. Trends Cancer. 2016;2(8):443-460. doi: 10.1016/j.trecan.2016.07.001 2. Del Gaizo MV, Brown JR, Certo M, Love TM, Novina CD, Letai A. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest. 2007;117(1):112-121. doi:10.1172/jci28281 3. Souers AJ, Leverson JD, Boghaert ER, et al. ABT-199, a potent and selective BCL-2… 
Sutimlimab: First Approval
TLDR
In February 2022, sutimlimab received its first approval in the USA to decrease the need for RBC transfusion due to haemolysis in adults with CAD.
The Complement System in the Central Nervous System: From Neurodevelopment to Neurodegeneration
TLDR
This review summarizes recent key findings regarding the role of different components of the complement system in health and pathology of the CNS and discusses the therapeutic potential of anti-complement strategies for the treatment of neurodegenerative conditions.

References

SHOWING 1-10 OF 19 REFERENCES
Inhibition of Complement C1s with Sutimlimab in Patients with Cold Agglutinin Disease (CAD): Results from the Phase 3 Cardinal Study
TLDR
The objective of the Cardinal study is to assess efficacy and safety of sutimlimab in adults with CAD who have a recent history of transfusion and quality of life (QOL) measured by the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale.
Sutimlimab in Cold Agglutinin Disease.
TLDR
In patients with cold agglutinin disease who received sutimlimab, selective upstream inhibition of activity in theclassic complement pathway rapidly halted hemolysis, increased hemoglobin levels, reduced bilirubin levels, and reduced fatigue coincided with inhibition of the classic complement pathway.
Cold agglutinin disease revisited: A multinational, observational study of 232 patients.
TLDR
In patients responding to rituximab-bendamustine, median response duration was not reached after 88 months, and estimated 5-year sustained remission was 77%.
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets
TLDR
The re-engineering of navitoclax is reported to create a highly potent, orally bioavailable and BCL-2–selective inhibitor, ABT-199, which inhibits the growth of BCL–dependent tumors in vivo and spares human platelets, indicating that selective pharmacological inhibition of Bcl-2 shows promise for the treatment of B CL-2-dependent hematological cancers.
Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial.
TLDR
Bendamustine-rituximab combination therapy is highly efficient, sufficiently safe, and may be considered in first line for patients with CAD requiring therapy.
Venetoclax for Patients With Chronic Lymphocytic Leukemia With 17p Deletion: Results From the Full Population of a Phase II Pivotal Trial.
TLDR
Venetoclax achieves durable responses and was well tolerated in patients with 17p deleted relapsed/refractory chronic lymphocytic leukemia and a high rate of blood MRD < 10-4 was achieved in this high-risk population.
Prophylactic use of eculizumab during surgery in chronic cold agglutinin disease
TLDR
A patient with CAD prone to exacerbation of haemolysis during acute phase reactions who was scheduled for cardiac surgery was treated prophylactically with eculizumab along with the usual perioperative precautions and aortic valve replacement was undertaken with full cardiopulmonary bypass at normothermia.
Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy.
TLDR
Venetoclax demonstrated promising clinical activity and favorable tolerability in patients with CLL whose disease progressed during or after idelalisib therapy, and achieved complete remission with incomplete bone marrow recovery.
Complement Activation and Inhibition in Autoimmune Hemolytic Anemia: Focus on Cold Agglutinin Disease.
TLDR
This review describes the complement-mediated hemolysis in AIHA with a major focus on CAD, in which activation of the classical pathway is essential and particularly relevant for complement-directed therapy.
Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737.
TLDR
This work exploited a novel functional assay that uses BCL2 homology domain 3 (BH3) peptides to predict dependence on antiapoptotic proteins, a strategy it calls BH3 profiling, and accurately predicts sensitivity to ABT-737 in primary chronic lymphocytic leukemia (CLL) cells.
...
...