Novel therapeutic agents for chronic myelomonocytic leukemia that are under development.
Authors | Year | Therapeutic agent | Mechanism | Subjects | Phase | Outcome |
---|---|---|---|---|---|---|
Padron |
2017 | Ruxolitinib | JAK1/2 inhibitor | CMML, 49 patients | I/II | ORR 46%, mOS 28 months (69 months from diagnosis) |
Ma |
2015 | Pacritinib | JAK2, CSF1, IRAK1 inhibitor | Preclinical | Combined with azacitidine, synergistic effect | |
Fenaux |
2007 | Tipifarnib | Farnesyltransferase inhibitor | High-risk MDS, 82 patients (19 patients with CMML) | II | CR rate 15% (3 patients with CMML), hematologic improvement 17%, mOS 11.7 months |
Patnaik |
2017 | Tipifarnib | Farnesyltransferase inhibitor | CMML, 24 patients | II | ORR 33% in wild-type RAS |
Borthakur |
2016 | Trametinib | MEK1/MEK2 inhibitor | Myeloid neoplasm, 97 patients (11 patients with CMML) | I/II | ORR 20% in cohort 1 (AML/MDS with RAS mutations); 3% in cohort 2 (AML/MDS/CMML with wild-type RAS); 27% in cohort 3 (CMML with RAS mutations) |
Patnaik |
2019 | Tagraxofusp (formerly SL-401) | Diphtheria toxin fused with interleukin-3 | CMML, 20 patients | I/II | Spleen response in 10 of 10 patients, BM CR in 3 patients |
Patnaik |
2020 | Lenzilumab | Anti-GM-CSF monoclonal antibody | CMML, 15 patients | I | Cumulative ORR 33.33%, better in RAS pathway mutant CMML |
Steensma |
2019 | H3B-8800 | SF3b complex inhibitor | Myeloid neoplasm, 84 patients (4 patients with CMML) | I | No objective CR or PR, decreased transfusion requirements in 14%, platelet response in 1 CMML patient |
Abbreviations: AML, acute myeloid leukemia; BM, bone marrow; CMML, chronic myelomonocytic leukemia; CR, complete response; MDS, myelodysplastic syndrome; mOS, median overall survival; ORR, overall response; PR, partial response.