Clin Cancer Res
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Multicenter Study
Phase Ib dose-escalation study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma.
Carfilzomib, a selective proteasome inhibitor, has shown safety and efficacy in relapsed and/or refractory multiple myeloma. This phase I study in patients with relapsed or progressive multiple myeloma assessed the safety and tolerability of escalating doses of carfilzomib in combination with lenalidomide and low-dose dexamethasone (CRd) to identify the dose for a phase II expansion study. ⋯ The maximum planned CRd dose, carfilzomib 27 mg/m(2), lenalidomide 25 mg, and dexamethasone 40 mg, was recommended for further study, with promising safety and efficacy.
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When diagnosed with cancer, patients can immediately make a meaningful positive impact on their health by stopping their tobacco use. Scientific evidence clearly shows that tobacco use in patients with cancer leads to poorer outcomes. ⋯ Therefore, both improved provision of cessation assistance to all patients with cancer who use tobacco or have recently quit and further study of the deleterious effects of tobacco use and benefits of tobacco cessation on cancer progression and treatment are needed and recommended by the American Association for Cancer Research. Progress on both fronts begins with universal assessment and documentation of tobacco use as a standard of quality cancer care regardless of treatment setting and will be further facilitated through the development of reliable, valid, and standard measures of tobacco use, incorporation of evidence-based procedures into quality and accreditation procedures, and the development of appropriate training, clinical infrastructure, and incentives for delivery of tobacco cessation interventions.
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The multikinase inhibitor sorafenib displays antitumor activity in preclinical models of osteosarcoma. However, in sorafenib-treated patients with metastatic-relapsed osteosarcoma, disease stabilization and tumor shrinkage were short-lived and drug resistance occurred. We explored the sorafenib treatment escape mechanisms to overcome their drawbacks. ⋯ mTORC2 activation is an escape mechanism from sorafenib treatment. When sorafenib is combined with everolimus, its antitumor activity is increased by complete inhibition of the mTOR pathway in the preclinical setting.
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Multiple myeloma is a usually incurable malignancy of plasma cells. New therapies are urgently needed for multiple myeloma. Adoptive transfer of chimeric antigen receptor (CAR)-expressing T cells is a promising new therapy for hematologic malignancies, but an ideal target antigen for CAR-expressing T-cell therapies for multiple myeloma has not been identified. B-cell maturation antigen (BCMA) is a protein that has been reported to be selectively expressed by B-lineage cells including multiple myeloma cells. Our goal was to determine if BCMA is a suitable target for CAR-expressing T cells. ⋯ BCMA is a suitable target for CAR-expressing T cells, and adoptive transfer of anti-BCMA-CAR-expressing T cells is a promising new strategy for treating multiple myeloma.