Real-world study on adoption of standard-of-care for transplant-eligible newly diagnosed multiple myeloma patients between 2017 and 2020/2021 across France, Germany, Spain, and Italy.

OBJECTIVES: This non-interventional observational study described the current standard-of-care for transplant-eligible newly diagnosed multiple myeloma (TE-NDMM) patients in France, Germany, Spain, and Italy, and recorded the evolution in regimen adoption in distinct elements of frontline treatment during 2017-2020/2021. METHODS: Clinical information on ongoing (I) or previous (II) TE-NDMM patients was extracted from the Cancerology database. Proportions of patients receiving regimens in each element and the evolution in regimen adoption were determined for the entire population and each country. RESULTS: Most common induction regimens among I patients were VRd in France (75.3%) and Spain (44.1%), VTd in Italy (65.2%), and regimens other than VRd/VTd/VCd in Germany. Maintenance was ongoing/planned for 78.3%, 62.3%, 65.2%, and 61.4% patients in France, Germany, Spain, and Italy, respectively. Among II patients, VRd induction increased from 27.0% in 2017 to 65.7% in 2019 in France, remained relatively low in Spain and Germany, and not present in Italy. In Italy and Spain, VTd induction declined from 72.4% and 58.3% in 2017 to 52.8% and 17.3% in 2019, respectively. VCd induction in Germany declined from 85.2% in 2017 to 64.1% in 2019. CONCLUSION: The use of bortezomib triplets in induction varied markedly over time and between selected countries.

Thymoquinone induces apoptosis in malignant T-cells via generation of ROS.

We show that HTLV-1 negative leukemia cells are more sensitive to TQ due to higher levels of drug-induced reactive oxygen species (ROS). PreG1 population in HTLV-1 negative Jurkat and CEM was higher than HTLV-1 transformed HuT-102 and MT-2 cells. Peripheral blood mononuclear cells were more resistant. Hoechst staining indicated more features of apoptosis, namely nuclear blebs and shrunken nuclei in HuT-102 than Jurkat. A greater depletion of the antioxidant enzyme glutathione occurred in Jurkat, which consequently led to an increase in ROS, loss of mitochondrial membrane potential, cytochrome c release, activation of caspases 3 and 9, and cleavage of PARP. Treatment with z-VAD-fmk partially reversed TQ-induced apoptosis, suggesting a caspase-dependent mechanism. N-acetyl cysteine prevented apoptosis providing evidence that cell death is ROS-dependent. Catalase prevented apoptosis to a lesser extent than NAC. In summary, TQ induces apoptosis in adult T cell leukemia/lymphoma by decreasing glutathione and increasing ROS, and levels of ROS underlie the differential cellular response to TQ. Our data suggest a potential therapeutic role for TQ in sensitizing HTLV-I-negative T-cell lymphomas.