[Values of Serum Ferritin, Folic Acid and Vitamin B12 in Treatment of Multiple Myeloma with Bortezomib Combined with Chemotherapy].

OBJECTIVE: To investigate the value of serum ferritin, folic acid and vitamin B12 in the treatment of multiple myeloma (MM) with bortezomib combined with chemotherapy. METHODS: Clinical data of 40 MM patients admitted to our hospital from January 2020 to August 2022 and 40 hematology outpatients during the same period were reviewed. All MM patients were treated with bortezomib combined with chemotherapy. The diagnostic efficacy of serum ferritin, folic acid and vitamin B12 on MM was analyzed by ROC curve. The changes of serum ferritin, folic acid and vitamin B12 in MM patients before and after treatment were compared. According to the mean values of serum ferritin, folic acid and vitamin B12, patients were divided into high and low expression groups, and the survival of patients between the groups was compared. RESULTS: Before treatment, the levels of serum ferritin and vitamin B12 in MM patients were significantly higher than those in control group, while folic acid was lower (all P <0.001). The area under the curve (AUC) of MM patients diagnosed with ferritin, folic acid and vitamin B12 were 0.928, 0.843 and 0.867, the specificity was 100%, 67.50% and 72.50%, and the sensitivity was 80.00%, 95.00% and 87.50%, respectively. After 4 cycles of chemotherapy, there were 9 cases of complete remission (CR), 19 cases of very good partial remission (VGPR), 6 cases of PR, 4 cases of stable disease (SD) and 2 cases of progression disease (PD) in 40 MM patients. In CR group, ferritin and vitamin B12 decreased but folic acid increased after treatment compared with before treatment (all P < 0.05). The overall survival (OS) rates of patients in low expression group of ferritin and vitamin B12 were significantly higher than those in high expression group (both P < 0.01). The OS rate of patients in high expression group of folic acid was significantly higher than that in low expression group (P < 0.01). Cox regression analysis showed that ferritin was an independent prognostic factor for MM patients (HR=8.850, 95%CI : 2.267-34.553, P =0.002). CONCLUSION: Serum ferritin, folic acid and vitamin B12 have some auxiliary value in the diagnosis and efficacy evaluation of MM, and ferritin is an independent prognostic factor for MM.

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients.

PURPOSE: Combinations of bortezomib (Velcade), cyclophosphamide and dexamethasone have shown significant efficacy and safety for patients of newly diagnosed multiple myeloma (NDMM). In this study, we compared the efficacy and safety of modified VCD regimens with novel changes in bortezomib dose and schedule for NDMM. METHODS: Eighty-five NDMM patients from multiple centers were randomly assigned to a high-dose (1.6 mg/m2) (group A) or a low-dose (1.3 mg/m2) (group B) bortezomib, administrated on days 1, 6, 11, and 16 subcutaneously in a 4-week cycle for nine cycles, combined with 40 mg dexamethasone on bortezomib days and cyclophosphamide 300 mg/m2 on days 1-3 intravenously. RESULTS: After four cycles, complete response (CR) or better in group A (43.6%) was higher than that in group B (12.8%) (P = 0.002). During induction, for patients with R-ISS stage III, the CR or better rate in group A was superior to that in group B (P = 0.01). Of patients < 65, the CR or better rate of group A was superior to that of group B (P = 0.004). Rapid onset of CR occurred in group A (P < 0.01). Meanwhile, rate of 3-4 diarrhea was higher in group A (P = 0.03), which caused higher rate of dose reduction for patients ≥ 65 (P = 0.041). No significant difference between the two groups in PFS and OS. CONCLUSIONS: The studied high-dose VCD as induction regimen had an improved CR rate, especially in patients < 65 or with R-ISS stage III, and is feasible for young and high-risk patients. Trial registration ClinicalTrials.gov: NCT02086942.

Modulating the function of ATP-binding cassette subfamily G member 2 (ABCG2) with inhibitor cabozantinib.

Cabozantinib (XL184) is a small molecule tyrosine kinase receptor inhibitor, which targets c-Met and VEGFR2. Cabozantinib has been approved by the Food and Drug Administration to treat advanced medullary thyroid cancer and renal cell carcinoma. In the present study, we evaluated the ability of cabozantinib to modulate the function of the ATP-binding cassette subfamily G member 2 (ABCG2) by sensitizing cells that are resistant to ABCG2 substrate antineoplastic drugs. We used a drug-selected resistant cell line H460/MX20 and three ABCG2 stable transfected cell lines ABCG2-482-R2, ABCG2-482-G2, and ABCG2-482-T7, which overexpress ABCG2. Cabozantinib, at non-toxic concentrations (3 or 5µM), sensitized the ABCG2-overexpressing cells to mitoxantrone, SN-38, and topotecan. Our results indicate that cabozantinib reverses ABCG2-mediated multidrug resistance by antagonizing the drug efflux function of the ABCG2 transporter instead of downregulating its expression. The molecular docking analysis indicates that cabozantinib binds to the drug-binding site of the ABCG2 transporter. Overall, our findings demonstrate that cabozantinib inhibits the ABCG2 transporter function and consequently enhances the effect of the antineoplastic agents that are substrates of ABCG2. Cabozantinib may be a useful agent in anticancer treatment regimens for patients who are resistant to ABCG2 substrate drugs.