Necrotizing periodontitis or medication-related osteonecrosis of the jaw (MRONJ) in a patient receiving Bemcentinib—a case report

Abstract

Bemcentinib is a newly developed AXL inhibitor that is currently under investigation in phase II trails for the treatment of acute myeloblastic leukemia (AML). Clinical and radiographic findings in this case were very similar to cases of MRONJ in patients receiving Sunitinib or other anti-angiogenetic substances, assuming that Bemcentinib may cause similar oral side effects. We present a male 81-year-old patient with a manifestation of alveolar bone necrosis at the central upper incisors following a 2-month regimen with the AXL-inhibitor Bemcentinib, administered for the treatment of secondary acute myeloblastic leukemia (sAML). Due to the duration of less than 8 weeks, the osteonecrosis was diagnosed as necrotizing periodontitis, but the intraoral clinical and radiographic findings were also compatible with the differential diagnosis of medication-related osteonecrosis of the jaw (MRONJ, stage II). Following to discontinuation of Bemcentinib, the affected bone was surgically revised including the removal of a demarcated bone sequester under preventive antibiotic treatment (metronidazole 400 mg t.i.d.). We hypothesize that Bemcentinib might increase the susceptibility for osteonecrosis of the jaw, probably related to its antiangiogenic effects and the resulting modulation of host immune response. Based on the current observations, it can be assumed that oro-dental health might be significant also prior and during treatment with Bemcentinib for the prevention of MRONJ.

Targeting CD301+ macrophages inhibits endometrial fibrosis and improves pregnancy outcome

“…To assess the efficacy of pharmacologic inhibition of the AXL pathway on endometrial fibrosis, a selective small molecule inhibitor against AXL, Bemcentinib, which has been used to perform clinical trials for treating cancers (Yule et al , 2018 ; Bumm et al , 2020 ), was given by oral administration (80 mg/kg, p.o., MedChemExpress; Holland et al , 2010 ; Lijnen et al , 2011 ) in an IUA mouse model. We performed two kinds of time points for the treatment: one begun 7 days later after the first curettage and one begun at the same day of the first curettage (Fig 7A and Appendix Fig S8 A).…”

Medication‐related osteonecrosis of the jaw: A disease of significant importance for older patients

“…13 Interestingly, MRONJ has been observed in patients with acute myelodysplastic leukemia treated with bemcentinib via an antiangiogenic mechanism and interference with the host immunological profile. 14 Owosho et al 15 have also reported cases of MRONJ, after ipilimumab, a monoclonal antibody administered in patients with malignant melanoma, and acts by inhibiting the immune system via CTLA-4 activation. Lastly, MRONJ has also been described after therapy surface of T-cells in a variety of cancers such as lung cancer.…”

“…MRONJ has also been associated with herceptin and pertuzumab, monoclonal antibodies administered in Her2‐positive breast cancer patients 13 . Interestingly, MRONJ has been observed in patients with acute myelodysplastic leukemia treated with bemcentinib via an anti‐angiogenic mechanism and interference with the host immunological profile 14 . Owosho et al 15 have also reported cases of MRONJ, after ipilimumab, a monoclonal antibody administered in patients with malignant melanoma, and acts by inhibiting the immune system via CTLA‐4 activation.…”

Targeting CD301+ macrophage inhibits endometrial fibrosis and improves pregnancy outcome

“…To assess the efficacy of pharmacologic inhibition of the AXL pathway on endometrial fibrosis, a selective small molecule inhibitor against AXL, Bemcentinib, which has been used to perform clinical trials for treating cancers (Yule, et al,2018;Bumm, et al,2020), was given by oral administration (80 mg/kg, p.o., MedChemExpress) (Holland, et al,2010;Lijnen, et al,2011) in an IUA mouse model. We performed two…”