Navtemadlin

Navtemadlin (KRT-232), an MDM2 inhibitor, showed efficacy in relapsed/refractory myelofibrosis and is now being tested in combination with ruxolitinib in the POIESIS trial. The study aims to improve outcomes for patients with suboptimal responses to ruxolitinib alone, targeting spleen and symptom improvements and disease modification.

Navtemadlin monotherapy showed safety and efficacy in relapsed/refractory myelofibrosis patients, with a 3-fold increase in spleen volume reduction (SVR35) and 2-fold increase in total symptom score reductions (TSS50) compared to best available therapy (BAT) in the BOREAS study. Treatment-emergent adverse effects were mostly grade 1 and 2, reversible, and predictable in onset and resolution. The POIESIS study will evaluate navtemadlin in sub-optimal responders.

Navtemadlin showed improved outcomes vs BAT in relapsed/refractory myelofibrosis, with a 3-fold increase in SVR35 and 2-fold increase in TSS50. GI and hematologic TEAEs were mostly grade 1/2, reversible, and predictable. The BOREAS study results suggest clinically relevant efficacy and safety, with the POIESIS study planned for sub-optimal responders.

Anne Sophie Michallet discusses ERADIC trial results comparing MRD-guided therapy with ibrutinib and venetoclax vs standard combination in intermediate-risk CLL, emphasizing defining best patient profile due to potential cardiologic toxicity.

Navtemadlin, a potent MDM2i, shows promise in treating myelofibrosis (MF) patients relapsed or refractory to JAKi therapy, with notable activity in bone marrow fibrosis reduction and driver mutation allele burden. The POIESIS trial (NCT06479135) aims to evaluate navtemadlin as an add-on to ruxolitinib in JAKi-naïve MF patients with suboptimal responses, seeking to improve SVR35 and TSS50 rates.

Navtemadlin monotherapy improved biomarkers of disease burden in relapsed/refractory myelofibrosis patients, including reductions in CD34 cells, driver mutation burden, serum inflammatory cytokine levels, and correlated with SVR, suggesting anti-clonal activity and disease modification.

Navtemadlin (KRT-232), an MDM2 inhibitor, reduced biomarkers of disease severity in R/R myelofibrosis patients, suggesting it targets disease-driving cells and alters progression. In the phase 3 BOREAS trial, navtemadlin showed significant reductions in CD34+ cells, driver gene VAF, and pro-inflammatory cytokines, correlating with spleen volume response and improved bone marrow fibrosis.

The NCCN Guidelines for myeloproliferative neoplasms (MPNs) have seen frequent updates since 2017, reflecting new approvals and treatment options. Aaron Gerds, MD, MS, emphasizes the importance of clinical trials and next-generation sequencing (NGS) in MPN management, highlighting the need for risk stratification to guide patient care and transplantation. Recent updates focus on clinical trials as preferred options over FDA-approved therapies and the use of NGS for higher-risk patients. Multiple phase 3 trials are underway, indicating a rapid evolution in MPN treatment.