The status of jaw lesions and medication-related osteonecrosis of jaw in patients with multiple myeloma.

BACKGROUND/PURPOSE: Myeloma jaw lesions are not uncommon. The study aimed to investigate the status of jaw lesions and medication-related osteonecrosis of jaw (MRONJ) in multiple myeloma (MM) patients. METHODS: One hundred and twenty-two consecutive newly-diagnosed MM patients seeking dental care at a hospital of southern Taiwan was examined according to jaw lesions with complete follow-up data. RESULTS: Median age of the patients was 67.8 years, and 88.5% of patients were of DS stage III and 41.0% were of ISS stage III at diagnosis. Median survival was 37.9 months for 43 (35.2%) patients with jaw lesions and 57.4 months for 79 patients without jaw lesions. 1-year, 5-year and >7-year overall survival rates for patients with jaw lesions versus patients without jaw lesions were 94.9%, 67.2%, 56.7% vs 83.7%, 51.8%, 26.8% respectively. Patients with jaw lesions had the worse survival (P = 0.03). Neither age nor stage affected survival. Jaw lesions involved the mandible more often than the maxilla and stopped progressing during remission, but did not repair. Jaw lesions were the first evidence or recurrent sign of MM in six (4.9%) patients. Long-term monthly antiresorptive therapy changed the radiographic patterns of jawbones and induced MRONJ developing in 16.7% (8/48) of patients. Five (62.5%) MRONJ sites spontaneously occurred without local risk factors. CONCLUSION: Nearly one-third of MM patients develop osteolytic jaw lesions that seem to be associated with poorer survival. Jaw lesion is an independent prognostic predictor of survival in myeloma. Antiresorptive drugs at less frequent dosing regimen are crucial to minimize spontaneous MRONJ.

A Phase II Study of Arginine Deiminase (ADI-PEG20) in Relapsed/Refractory or Poor-Risk Acute Myeloid Leukemia Patients.

Exogenous arginine is required for growth in some argininosuccinate synthetase (ASS)-deficient cancers. Arginine deiminase (ADI) inhibits growth in various ASS-deficient cancers by depleting arginine. The efficacy of pegylated ADI (ADI-PEG20) in relapsed/refractory/poor-risk acute myeloid leukemia (AML) was evaluated in 43 patients in a prospective, phase II trial (NCT01910012 (10/07/2013), https://clinicaltrials.gov/ct2/show/NCT01910012?term = ADI-PEG20&rank = 12 ). Despite almost all pre-treatment tumor samples showing ASS deficiency, the best response among 21 evaluable patients was complete response (CR) in 2 (9.5%) and stable disease in 7 (33.3%), yielding a disease control rate (DCR) of 42.9%. The response durations of the two patients with CR were 7.5 and 8.8 months. DCR was correlated with a median of 8 weeks of arginine depletion to ≤10 µM. Using whole transcriptome sequencing, we compared gene expression profiling of pre- and post-treatment bone marrow samples of the two responders and three non-responders. The expression levels of some markers for AML subtypes and c-MYC regulated genes were considered potential predictors of response to ADI-PEG20. These results suggest that ASS deficiency is a prerequisite but not a sufficient condition for response to ADI-PEG20 monotherapy in AML. Predictive biomarkers and mechanistic explorations will be critical for identifying appropriate patients for future AML trials of ADI-PEG20.