The changing role of high dose melphalan with stem cell rescue in the treatment of newly diagnosed multiple myeloma in the era of modern therapies—back to the future!
Publication date: Available online 17 January 2020Source: Best Practice &Research Clinical HaematologyAuthor(s): Dickran Kazandjian, Alexander Dew, Elizabeth HillAbstractState of the art treatment for myeloma involves using 3-drug combinations incorporating immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). Clinical trials for 4-drug combinations incorporating monoclonal antibodies added to IMiD and PI based backbones are underway. Recent retrospective analyses show that patients who attain MRD negativity have similar long term outcomes regardless of early or delayed high dose melphalan with autologous stem cell support (HDM-ASCT). Given HDM-ASCT toxicity, not “overtreating” would be beneficial. Short of data from future prospective clinical trials addressing the question of the role of HDM-ASCT in MRD negative patients, varying expert opinions inherently arise. In this paper, we present the historical context of HDM-ASCT and data supporting 3-drug combinations. We then propose that a viable option for patients who reach MRD negativity is to transition to maintenance therapy directly without early HDM-ASCT, and reserving stem cell harvest to cases where HDM-ASCT is a possibility at relapse.
ConclusionHigh-dose chemotherapy and autologous stem cell transplant using TBC conditioning for both PCNSL and secondary CNS non-Hodgkin lymphoma appears to have encouraging long term efficacy with manageable side effects.
ConclusionT2B2F is associated with a higher incidence of acute GVHD compared with T1B2F. These results suggest that a lower dose-intensity of thiotepa and busulfan in the TBF regimen may yield better results in patients with AML in CR.
Conclusion Multiple myeloma patients who received HDC/ASCT demonstrated a significant decrease in 18FDG uptake in the supratentorial brain and cerebellum, while patients who received CDC did not demonstrate significant changes in the brain 18FDG uptake.
We retrospectively analyzed 48 CNS lymphoma patients who received HDC/ASCT using TBC conditioning. We found a 2-year PFS and OS rate of 80.5% and 80.1%, respectively. Toxicities included nausea/vomiting, diarrhea, mucositis, and febrile neutropenia. Treatment-related mortality was 8.3% in the first 100 days post-transplant. This data supports the use of consolidative ASCT in PCNSL and secondary CNS lymphoma patients.
The study is evaluating daratumumab plus lenalidomide, bortezomib, and dexamethasone in autologous stem cell transplant eligible patients newly diagnosed with multiple myeloma.
Bone Marrow Transplantation, Published online: 17 February 2020; doi:10.1038/s41409-020-0829-1LDH and renal function are prognostic factors for long-term outcomes of multiple myeloma patients undergoing allogeneic hematopoietic stem cell
Bargou Andreas Rosenwald Thorsten Stühmer Ellen Leich Approximately 20% of multiple myeloma (MM) cases harbor a point mutation in KRAS. However, there is still no final consent on whether KRAS-mutations are associated with disease outcome. Specifically, no data exist on whether KRAS-mutations have an impact on survival of MM patients at diagnosis in the era of novel agents. Direct blockade of KRAS for therapeutic purposes is mostly impossible, but recently a mutation-specific covalent inhibitor targeting KRASp.G12C entered into clinical trials. However, other KRAS hotspot-mutations exist in MM patients, incl...
Patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome are currently treated with therapeutic options for multiple myeloma, and this disease is a treatable disease. Accurate diagnosis and proper treatment in the early stage of the disease are essential to further improve prognosis. This review focuses on diagnosis, treatment and the current status of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome in Japan. AbstractPolyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome is a rare ...
Giavaresi Alessandro Osteolytic bone disease is the major complication associated with the progression of multiple myeloma (MM). Recently, extracellular vesicles (EVs) have emerged as mediators of MM-associated bone disease by inhibiting the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Here, we investigated a correlation between the EV-mediated osteogenic inhibition and MM vesicle content, focusing on miRNAs. By the use of a MicroRNA Card, we identified a pool of miRNAs, highly expressed in EVs, from MM cell line (MM1.S EVs), expression of which was confirmed in EVs from bone marrow (BM) p...