The use of Novel Oral Anticoagulants in Cancer Patients with Venous Thromboembolism: A Review
Venous thromboembolism (VTE) is not uncommon among patients with cancer and is one of the major causes of mortality and morbidity. Treatment with low molecular weight heparin (LMWH) is effective, yet accompanied by the need for daily administration of injections for a prolonged time and (even rarely) thrombocytopenia. The discovery of novel oral anticoagulants (NOACs) was based on an effort to improve the pharmacodynamic and pharmacokinetic properties of previous generation anticoagulants while maintaining efficacy without the need for daily subcutaneous administration and frequent laboratory monitoring. (Source: Seminars in Oncology)
Source: Seminars in Oncology - November 17, 2016 Category: Cancer & Oncology Authors: S. Karakatsanis, A. Roumpi, K.N. Syrigos Source Type: research
PI3K signaling pathway in normal B cells and indolent B-cell malignancies
In chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHLs), B-cell receptor signaling leads to activation of the phosphatidylinositol 3-kinase (PI3K) pathway. Idelalisib, a PI3K δ inhibitor was approved in 2014 by the US Food and Drug Administration (FDA) in combination with rituximab for the treatment of patients with CLL for whom single-agent rituximab would be considered appropriate and as a single agent for patients with relapsed small lymphocytic lymphoma (SLL) and re lapsed follicular lymphoma (FL). (Source: Seminars in Oncology)
Source: Seminars in Oncology - November 16, 2016 Category: Cancer & Oncology Authors: Georgios Pongas, Bruce D. Cheson Source Type: research
PI3K Signaling Pathway in Normal B Cells and Indolent B Cell Malignancies
In chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHL), B cell receptor signaling leads to activation of the PI3K pathway. Idelalisib, a PI3K δ inhibitor was approved in 2014 by the US Food and Drug Administration (FDA) in combination with rituximab for the treatment of patients with CLL for whom single agent rituximab would be considered appropriate and as a single agent for patients with relapsed small lymphocytic lymphoma (SLL) and re lapsed follicular lymphoma (FL). Following its approval, several trials investigating various PI3Kδ inhibitors as single agents or in combination with chemoimmunotherapy o...
Source: Seminars in Oncology - November 16, 2016 Category: Cancer & Oncology Authors: Georgios Pongas, Bruce D. Cheson Source Type: research
Optimal Treatment Strategies in Myeloma: An Argument Against Maintenance Therapy after Autologous Stem Cell Transplantation
Despite continuing advancements in novel therapeutics for Multiple Myeloma (MM), high-dose therapy with autologous stem cell rescue continues to represent the standard approach to treat transplant-eligible, newly diagnosed patients [1]. As the disease remains essentially incurable, and median progression-free survivals after autologous transplant are measured in years and not decades, attempts to improve outcomes in the post-transplant setting have been extensive and commonly focused on a “maintenance” approach. (Source: Seminars in Oncology)
Source: Seminars in Oncology - November 15, 2016 Category: Cancer & Oncology Authors: Joshua Richter, Noa Biran, David Vesole, David Siegel Tags: Mailankody: Myeloma Source Type: research
A Look Backward and Forward in the Regulatory and Treatment History of Multiple Myeloma: Approval of Novel-Novel Agents, New Drug Development, and Longer Patient Survival
The past decade has seen significant advances in our understanding and treatment of multiple myeloma (MM) and its precursor diseases. These advances include gains in knowledge of the underlying pathobiology including molecular and cellular prognostic factors for disease progression. In parallel we have witnessed the availability of novel therapeutics. Together these advances have translated into improvements in long-term clinical benefit and survival in MM. Indeed, it has been shown that patients diagnosed in the last decade have experienced almost doubling of median survival time [1]. (Source: Seminars in Oncology)
Source: Seminars in Oncology - November 15, 2016 Category: Cancer & Oncology Authors: Dickran Kazandjian, Ola Landgren Source Type: research
Management of Multiple Myeloma in Resource-Constrained Settings
A 54-year-old man is referred to your clinic for evaluation of elevated serum total protein (8.8 gm/dL) noted on routine labs recently. Additional evaluation included a serum protein electrophoresis, which revealed a monoclonal spike in the gamma region measuring 3.2 gm/dL, and a corresponding serum immunofixation confirm IgG kappa monoclonal protein. Serum free kappa was elevated at 34 mg/dL and the free lambda was 0.61 mg/dL for an elevated kappa/lambda ratio of 55.7. Serum IgA and IgM levels were low. (Source: Seminars in Oncology)
Source: Seminars in Oncology - November 15, 2016 Category: Cancer & Oncology Authors: Lalit Kumar, Ranjit Kumar Sahoo Source Type: research
Recommend upfront consolidation with high-dose melphalan and autologous stem cell support
The overall goal of treatment for multiple myeloma (MM) is to prolong survival for as long as possible with the minimal treatment burden for each patient. Consolidation with upfront high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT) can prolong progression-free and overall survival by deepening response. It thereby can improve quality of life by allowing patients to have a time on maintenance therapy along with infrequent office visits, making it cost-effective in many situations. (Source: Seminars in Oncology)
Source: Seminars in Oncology - November 14, 2016 Category: Cancer & Oncology Authors: Gunjan L. Shah, Sergio A. Giralt Source Type: research
Management option 1: Recommend upfront consolidation with high-dose melphalan and autologous stem cell support
The overall goal of treatment for multiple myeloma (MM) is to prolong survival for as long as possible with the minimal treatment burden for each patient. Consolidation with upfront high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT) can prolong progression-free and overall survival by deepening response. It thereby can improve quality of life by allowing patients to have a time on maintenance therapy along with infrequent office visits, making it cost-effective in many situations. (Source: Seminars in Oncology)
Source: Seminars in Oncology - November 14, 2016 Category: Cancer & Oncology Authors: Gunjan L. Shah, Sergio A. Giralt Source Type: research
Management Option 1: Recommend Upfront Consolidation with High dose Melphalan and Autologous Stem Cell Support
56 year old man with ISS Stage II multiple myeloma and 70% plasma cell infiltration in the bone marrow and normal cytogenetics returns after completing 6 cycles of induction therapy. On laboratory evaluation, the patient has no monoclonal protein on serum and urine electrophoresis and immunofixation and the free light chain ratio is within normal limits. A bone marrow biopsy reveals normal trilineage hematopoiesis with less than 5% plasma cells. Multicolor flow cytometric analysis of the bone marrow aspirate reveals minimal residual disease (MRD) (sensitivity 1 in 105). (Source: Seminars in Oncology)
Source: Seminars in Oncology - November 14, 2016 Category: Cancer & Oncology Authors: Gunjan L. Shah, Sergio A. Giralt Source Type: research
The High Cost of Ignorance in Oncology
With this issue of Seminars in Oncology we experiment with a different approach. We move away from the traditional format of having an entire issue dedicated to one topic, to fewer papers focused on one topic. We dedicate a substantial effort to multiple myeloma (MM) an interesting disease whose treatment is evolving and bring you additional manuscripts covering interesting and timely topics. An example of the latter is the thought-provoking contribution form PHARMAC in New Zealand. At a time when discussions about drug costs leads to agreement “this trajectory is not sustainable” but provide no clear solutions, PHARMA...
Source: Seminars in Oncology - November 14, 2016 Category: Cancer & Oncology Authors: Tito Fojo Source Type: research
Treatment of High-Risk Smoldering Myeloma
Multiple Myeloma (MM) is almost always preceded by a precursor disease state [1]. Smoldering myeloma (SMM) is a precursor disease defined by clinical and histopathological features (absence of myeloma defining biomarkers or end organ damage and bone marrow plasma cells (BMPC) ≥10% or monoclonal protein ≥3 g/dL). Traditionally, SMM is approached with careful routine monitoring. First, I must disclose that my general practice is to treat SMM patients within the context of clinical trials. For high-risk SMM patients not eligible for clinical trials, I continue to observ e patients until they meet updated International Mye...
Source: Seminars in Oncology - November 13, 2016 Category: Cancer & Oncology Authors: Neha Korde Source Type: research
Deferring Autologous Stem Cell Transplantation for Consolidation of Minimal Residual Disease in Multiple Myeloma
Despite the complex clonal heterogeneity of multiple myeloma (MM), modern induction therapy can induce meaningful responses in as many as 70% of patients, and the expanding treatment landscape can also prolong survival in the relapsed/refractory setting [1,2]. In order to identify patients who achieve deeper responses to antimyeloma therapy, highly sensitive assays to detect minimal residual disease (MRD) have been deployed [3,4]. As a result, in 2016 the International Myeloma Working Group revised response criteria to include MRD negativity by multiparameter flow cytometry (MFC) in the definition of stringent complete res...
Source: Seminars in Oncology - November 10, 2016 Category: Cancer & Oncology Authors: Marc Braunstein, Ruben Niesvizky Source Type: research
Multiple myeloma epidemiology and survival: A unique malignancy
Multiple myeloma (MM), although a rare disease, is the second most common hematologic malignancy. It is found in the spectrum of plasma cell dyscrasias, which begins with monoclonal gammopathy of unknown significance (MGUS) to overt plasma cell leukemia and extramedullary myeloma. MM is associated with significant morbidity due to its end-organ destruction. It is a disease of the older population and its incidence in the African American population is twice that of the European American population. (Source: Seminars in Oncology)
Source: Seminars in Oncology - November 9, 2016 Category: Cancer & Oncology Authors: Dickran Kazandjian Source Type: research
Multiple Myeloma Epidemiology and Survival, a Unique Malignancy
Multiple myeloma (MM), although a rare disease, is the second most common hematologic malignancy. It is found in the spectrum of plasma cell dyscrasias which begins with monoclonal gammopathy of unknown significance to overt plasma cell leukemia and extramedullary myeloma. MM is associated with significant morbidity due to its end-organ destruction. It is a disease of the older population and its incidence in the African American population is twice that of the European American population. Improvements in the treatment of MM in the past couple of decades, beginning with the use of autologous stem cell transplantation foll...
Source: Seminars in Oncology - November 9, 2016 Category: Cancer & Oncology Authors: Dickran Kazandjian Source Type: research
Combination Therapy for Fit (Younger and Older) Newly Diagnosed Multiple Myeloma Patients: Data Support Carfilzomib, Lenalidomide and Dexamethasone Independent of Cytogenetic Risk Status
I was given the task of supporting the use of carfilzomib, lenalidomide and dexamethasone (KRd) as therapy for patients with a new diagnosis of multiple myeloma (MM). I will argue KRd is well in line with modern treatment goals for MM: rapid, deep and sustainable treatment effect, with limited toxicity. Based on available data on its efficacy and safety profile, in the U.S., I would conjecture KRd will replace bortezomib, lenalidomide and dexamethasone (RVd) as the standard of care for “fit patients” with a new diagnosis of MM [1]. (Source: Seminars in Oncology)
Source: Seminars in Oncology - November 9, 2016 Category: Cancer & Oncology Authors: Ola Landgren Source Type: research
