Clinical advances in hematology & oncology : H&O
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Multiple myeloma (MM) is a disorder of clonal plasma cells that accumulate in the bone marrow and secrete a monoclonal protein detectable in the blood and/or urine. In the last decade, the outcome of patients with MM has markedly improved owing to the introduction of agents such proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide, lenalidomide) as induction, consolidation, and maintenance strategies. ⋯ In this review, we will describe the most promising new approaches to treat MM, including those based on targeting protein homeostasis, enhancing anti-MM immunity, targeting MM with monoclonal antibodies and immunotoxins, modulating bone metabolism, targeting histone modifications, targeting genomic instability and cell cycle alterations, and the use of genomic profiling to provide personalized therapies. These advances will continue to transform MM into a chronic illness, and have curative potential.
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Clin Adv Hematol Oncol · Oct 2014
ReviewPlatinum agents in the treatment of early-stage triple-negative breast cancer: is it time to change practice?
Triple-negative breast cancer (TNBC) carries a higher risk of distant recurrence and death in the first 5 years compared with other types of breast cancer. Owing to the largely heterogeneous nature of TNBC, no unifying alteration exists that could benefit from a specific targeted therapy. ⋯ The utility of platinum agents in addition to standard adjuvant or neoadjuvant chemotherapy remains controversial, however, because data on overall survival and disease-free survival are not available. It remains unclear whether the addition of platinum agents to neoadjuvant chemotherapy improves long-term outcomes of TNBC.
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Clin Adv Hematol Oncol · Apr 2014
ReviewSelective Bcl-2 inhibition to treat chronic lymphocytic leukemia and non-Hodgkin lymphoma.
ABT-199, a second-generation BH3 mimetic, is an orally bioavailable, small molecule inhibitor that selectively targets B-cell lymphoma/leukemia 2 (Bcl-2). Bcl-2 is a key protein that inhibits the intrinsic mitochondrial pathway of apoptosis. First-generation BH3 mimetics such as navitoclax (ABT-263) had a broad range of inhibitory activity against Bcl-2 family members, including Bcl-2, Bcl-XL, and Bcl-w. ⋯ This selectivity has been consistent with the early results of the ongoing phase 1 clinical trial of ABT-199 in which the drug has demonstrated high rates of activity in relapsed/refractory CLL and NHL without dose-dependent thrombocytopenia. On-target tumor lysis syndrome (TLS) has been observed in a subset of patients treated with ABT-199, but changes in initial dosing and stepwise dose escalation have now been implemented to mitigate this risk. Ongoing correlative studies are being performed to help identify patients with the highest chance of response and the greatest risk for TLS.