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.
Highlights
The idea of developing an extensive arsenal of active substances for targeted and individual cancer therapy has produced an array of anti-angiogenetic active substances, e.g., Sunitinib [1,2,3,4], that might induce medication-related osteonecrosis of the jaw as a side effect
An 81-year-old male patient with a diagnosis of secondary acute myeloblastic leukemia treated with the AXL inhibitor Bemcentinib for 2 months as part of a phase II trail was referred to the outpatient clinic of the Department of Conservative Dentistry and Periodontology, University Hospital Munich due to exposed alveolar bone of the upper anterior jaw persisting for approximately 4–5 weeks in June 2019
Regarding the pathogenesis of bone necrosis associated with Medication-related osteonecrosis of the jaw (MRONJ), different etiologic models have been intensively discussed considering mainly the effects of bisphosphonates [1, 4]
Summary
The idea of developing an extensive arsenal of active substances for targeted and individual cancer therapy has produced an array of anti-angiogenetic active substances, e.g., Sunitinib [1,2,3,4], that might induce medication-related osteonecrosis of the jaw as a side effect. An 81-year-old male patient with a diagnosis of secondary acute myeloblastic leukemia (sAML) treated with the AXL inhibitor Bemcentinib for 2 months as part of a phase II trail was referred to the outpatient clinic of the Department of Conservative Dentistry and Periodontology, University Hospital Munich due to exposed alveolar bone of the upper anterior jaw persisting for approximately 4–5 weeks in June 2019. The exposed bone appeared necrotic due to grey discoloration and was mobile upon gentle probing indicating partial demarcation and sequestration. Both incisors showed gingival recession defects > 6 mm at the mesial aspects of the tooth root (Fig. 1a, b). Histopathological examination of the surgically removed tissue depicted in Fig. 1j confirmed the clinical findings by revealing necrotic bone with inflammatory cell infiltrate and gram-positive, rod-shaped bacteria (Fig. 2a–d)
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