Humanigen Inc (fka HGENQ)

[Knuckle Sandwich]

Phase 1 study of lenzilumab, a recombinant anti–human GM-CSF antibody, for chronic myelomonocytic leukemia

In summary, we report the first study of lenzilumab in CMML and document that the drug is well tolerated, without any drug-related grade 3-4 AEs. Durable clinical benefit was achieved in 33% of patients, and 1 patient with a partial marrow response was bridged to an allogeneic hematopoietic stem cell transplantation, providing proof of concept that GM-CSF inhibition is a viable therapeutic strategy in CMML. Responses were seemingly better in RAS pathway–mutant CMML patients and in those who demonstrated GM-CSF hypersensitivity in colony-forming assays and robust PDX engraftment (both are innate features of RAS pathway–mutant CMML). Similar GM-CSF hypersensitivity is seen in juvenile myelomonocytic leukemia, a pediatric MDS/MPN overlap neoplasm that is driven largely by germline and somatic RAS pathway mutations (bona fide RASopathy), with poor outcomes.11 Future studies are warranted to identify CMML patient subtypes who are more likely to respond (eg, CMML patients with RAS pathway mutations and/or those with GM-CSF hypersensitivity in colony-forming assays), to identify rational combination strategies and to test the safety and efficacy of lenzilumab in children with juvenile myelomonocytic leukemia.

https://ashpublications.org/blood/article/136/7/909/454390/Phase-1-study-of-lenzilumab-a-recombinant