Impact of early reduction in paraprotein on survival in transplant ineligible myeloma: Lesson from a tertiary cancer center in rural India

Introduction: The impact of rapid reduction in paraprotein levels, with induction chemotherapy in myeloma, on treatment outcomes is less clear. There are very few studies in transplant ineligible patients treated with novel agents, correlating an early reduction in paraprotein with survival duration. Methods: In this retrospective analysis of newly diagnosed multiple myeloma, ineligible for stem cell transplant, paraprotein levels at baseline and 3 months were noted with percentage reduction. Survival analysis was performed with Kaplan–Meier curves and Cox proportional hazard model. Results: Among a total of 121 patients, 42 (35%), 29 (24%), and 50 (41%) had paraprotein reduction of 100%, 90%–99%, and <90%, respectively from baseline levels at 3 months. Patients with complete disappearance of paraprotein (100% reduction) when compared against those with <100% reduction at 3 months had a trend toward higher overall survival (OS) (3-year OS of 81% vs. 69%, hazard ratio [HR] = 0.54, P = 0.182). However, the progression-free survival (PFS) was significantly higher when these two groups were compared (median PFS of 51 vs. 17 months, HR = 0.33, P ≤ 0.001). When patients with ≥90% reduction were compared with <90% reduction at 3 months, there was significant improvement in both OS and PFS (3-year OS of 80% vs. 48%, HR = 0.24, P = 0.001, median PFS of 38 vs. 14 months, HR = 0.13, P < 0.001). Conclusions: Achieving a faster and deeper reduction in paraprotein as early as 3 months could lead to significant improvement in PFS

Will the first-line induction therapy of bortezomib for newly diagnosed multiple myeloma be challenged in the era of novel drugs? / 白血病·淋巴瘤

For newly diagnosed multiple myeloma (MM) patients, bortizomib based on chemotherapy has achieved desirable complete remission rate, good progression-free survival and overall survival, which is now a first-line choice in both transplant-eligible and transplant-ineligible patients. In recent years, other new treatment options such as proteasome inhibitors , immunomodulators , monoclonal antibody and cellular immunotherapy have posed a challenge to the first-line therapeutic status of bortizomib because of their favorable efficacy and safety. Oral proteasome inhibitor or monoclonal antibody combined with immunomodulators and dexamethasone might become the first-line induction therapy of newly-diagnosed MM patients. Moreover, chimeric antigen receptor T-cell immunotherapy (CAR-T) may also play a role in the first-line treatment, especially for the induction therapy of high-risk patients and the consolidation treatment of the elimination in minimal residual disease.

Maintenance therapy for multiple myeloma in the era of novel agents:reports from the 57th American Society of Hematology annual meeting / 白血病·淋巴瘤

Despite many recent advances in the treatment of multiple myeloma (MM), the course of the disease is characterized by a repeating pattern of periods of remission and relapse as patients cycle through the available treatment options. Evidence is mounting that long-term maintenance therapy may help suppressing residual disease after definitive therapy, prolonging remission and delaying relapse. For patients undergoing autologous stem cell transplantation (ASCT), lenalidomide maintenance therapy has been shown to improve progression-free survival (PFS), however, it is still unclear whether this translates into extended overall survival (OS). For patients ineligible for ASCT, continuous therapy with lenalidomide and low-dose dexamethasone is shown to improve PFS and OS (interim analysis) compared with a standard, fixed-duration regimen of melphalan, prednisone, and thalidomide in a large phase Ⅲ trial. Other trials have also investigated thalidomide and bortezomib maintenance for ASCT patients, and both agents have been evaluated as continuous therapy for those who are ASCT ineligible. However, some important questions regarding the optimal regimen and duration of therapy must be answered by prospective clinical trials before maintenance therapy, and continuous therapy should be considered routine practice. This article reviewed the available data on the use of maintenance or continuous therapy strategies and highlights ongoing trials reported in the 57th American Society of Hematology (ASH) annual meeting that would help to further define the role of these strategies in the management of patients with newly diagnosed MM.

Advances in the treatment of multiple myeloma: reports from the 56th American Society of Hematology annual meeting / 白血病·淋巴瘤

Multiple myeloma (MM) is the second most common hematological malignancy.In the 56th American Society of Hematology (ASH) annual meeting,there are mainly five hot and key topics focusing on development of MM treatment,including when is the opportunity of transplant-eligible patients in the era of novel therapy? Should continuous therapy be the standard therapeutic approach in MM? What is a practical approach to relapsed MM? How should the recurrence/refractory MM patients be managed and treated? And what are the approved agents and novel agents?

Goals for the treatment of multiple myeloma in the era of novel agents / 中国肿瘤临床

The treatment of multiple myeloma has become possible in the era of novel agents. Novel agents have dramatically improved the response rates of multiple myeloma (MM) and have extended the survival of patients even if MM remains an incurable disease. De-termining the treatment goals of MM has become a major challenge for clinicians in the era of novel agents. Many results show the correlation between response depth and patients' survival. Complete remission (CR), stringent CR, phenotypic CR, and CRs at the molecular and PET-CT levels are being explored and becoming the goals of MM treatment. Doctors should balance efficacy with adverse effects in daily clinical practice to avoid the blind pursuit of a high and deep response rate.

The impact of novel therapeutic agents before and after frontline autologous stem cell transplantation in patients with multiple myeloma

BACKGROUND: Novel agents (NAs) such as thalidomide and bortezomib have been administered in combination with autologous stem-cell transplantation (ASCT) to effectively treat multiple myeloma (MM). However, whether NAs perform better as induction treatments prior to transplantation, or as post-transplant maintenance therapies remains unclear. METHODS: We retrospectively analyzed 106 consecutive patients with MM who underwent ASCT within 1 year of diagnosis as first-line therapy. RESULTS: Eighty-seven (82.1%) patients received NAs before ASCT, whereas 68 (64.2%) received NAs after ASCT. NAs were administered to each patient as follows: before ASCT alone (N=29, 27.4%), after ASCT alone (N=10, 9.4%) or both before and after ASCT (N=58, 54.7%). High-quality rates before and after ASCT were significantly higher for patients who received NAs as induction treatment compared to those who did not receive pre-transplant NAs. At a median follow-up of 37.9 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 42.8% and 70.2%, respectively. The PFS and OS were significantly higher in patients with NAs as post-transplant maintenance treatment (P=0.03 and P=0.04, respectively), but not in those with NAs as pre-transplant induction treatment. The PFS of patients with NAs before and after ASCT was higher than that of the patients with NAs as induction therapy alone (P=0.05). Age, serum beta2-microglobulin level, complete response after ASCT, and NA use post-ASCT independently predicted survival outcomes. CONCLUSION: These findings suggest that integration of NAs post-ASCT could benefit patients with MM undergoing ASCT. Induction therapy using NAs also improves high-quality response rates before and after ASCT.

Treatment strategies for relapsed/refractory multiple myeloma / 白血病·淋巴瘤

Multiple myeloma is a malignancy of plasma cells,which is still incurable now.Despite dramatic improvement of the response rate and overall survival have been made due to the application of target therapy and stem cell transplantation,the treatment effect is difficult to maintain,nearly all patients will eventually relapse and become refractory.At relapse,the challenge is to select the appropriate treatment for each patient.The decision will be both disease-dependent and patient-dependent.

Novel cardiovascular drugs in clinical trials.

Cardiovascular diseases remain a major cause of morbidity and mortality worldwide, regardless of the recent advances in medical and surgical treatment, for as life expectancy in the developed countries increases, cardiovascular conditions affecting the elderly also rises. Atherosclerosis and cardiovascular diseases take a huge toll on the society, making them the leading cause of death in developed countries. Phenomenal advances in the pathophysiology of cardiovascular disease and the molecular signaling pathways has revealed the role of endothelial dysfunction involved therein and thus has raised the possibility of novel therapeutic targets. Such potential cellular targets include the vascular smooth muscle cells, monocyte/macrophage cell lines, platelets, and endothelial cells. Certain studies affirm that antiplatelet agents, antioxidant therapies, amino acid supplementation, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers may prevent or slow the progression of the disease process. The race is on for new medicines that can treat and prevent heart attacks and strokes, arising out of atherosclerosis, which kills nearly 1 million people a year in the U.S.A alone.

The Molecular Targets for the Diagnosis and Treatment of Pancreatic Cancer

Pancreatic cancer is considered an aggressive malignancy that responds poorly to current treatments and therefore has a dismal survival rate. This disease is usually not diagnosed until a late stage, at which point palliative chemotherapy with the purine analogue gemcitabine and/or a fluoropyrimidine or a platinum agent is the standard approach. There are some new data on the molecular and genetic changes that take place in pancreatic cancer, which may facilitate the accuracy of diagnosis and efficacy of treatments. However, translational efforts in clinical practice have increased clinicians' options with a targeted agent, erlotinib, in combination with the standard gemcitabine chemotherapy. Many other novel drugs currently being tested in the field of pharmaco-oncology target various altered biological pathways and molecules. Nevertheless, the lack of clinically significant improvements in treatments is rendering efforts to develop methods of early diagnosis both more urgent and promising. The aim of this review was to summarize the molecular basis of pancreatic carcinogenesis and the latest developments in diagnosis by molecular means, focusing on the results of clinical research into targeted and personalized treatments.