1,721,069 research outputs found
Novel Experimental Drugs for Treatment of Multiple Myeloma
No full text: Multiple myeloma (MM) is the second most frequent hematological malignancy characterized by bone marrow aberrant plasma cells proliferation leading to a genetic complex and heterogeneous disease, with a median survival ranging from two to more than 10 years. By using new drugs such as proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs) in different combinations and high-dose therapy followed by auto-transplantation, there has been an amazing improvement in the outcome of this disease in recent years. Despite this, MM is still considered an incurable disease, characterized by remission periods alternated with relapse/progression episodes finally leading to resistant disease. In particular, patients who become refractory to PIs, IMiDs and mAbs have a very poor outcome. Moreover, to overcome resistant residual disease, a large combination of drugs will be increasingly used in early lines of therapy; this further reduces the therapeutic options at each relapse. This natural history means that MM always needs new drugs/strategies to overcome the incoming resistance. New combinations of naked mAbs are becoming the therapy of choice for patients refractory to lenalidomide and/or PI; conjugated mAbs will be useful in triple- and more-refractory patients; CAR-T cells and bispecific mAbs have shown relevant results in very advanced stages of disease. In this review, we reported the results of these new therapies and explored their potential applications. Personalized and precision medicine seem to be the new frontier of cancer treatment. Although no single or few factors have been identified as disease drivers in MM, recurrent gene mutations were recognized and specific compounds targeting these alterations were developed and studied. Therefore, we reviewed these targeted drugs to try to understand what the best therapeutic strategy in MM is
Belantamab Mafodotin for the Treatment of Multiple Myeloma: An Overview of the Clinical Efficacy and Safety
Full text linkDespite the introduction of immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and, more recently, monoclonal antibodies (mAbs), in the chemotherapy regimens for newly diagnosed (NDMM) and relapsed/refractory MM (RRMM), the occurrence of drug resistance remains a challenge in MM patients. This is mainly in the advanced stage of the disease when treatments are limited, and the prognosis is abysmal. Nevertheless, novel molecules and therapeutic approaches are rapidly moving through the several phases of drug development and could address the need for new treatment options. The recent innovative B-cell maturation antigen (BCMA) targeted immunotherapies, such as belantamab mafodotin, the first-in-class monoclonal antibody-drug conjugate (ADC), induce an effective and durable response in triple-class refractory disease and to be approved in MM. In contrast with the other BCMA-targeted therapies as CAR T cells with a complex manufacturing process, and bispecific antibodies, both requiring inpatient hospitalization to monitor the occurrence of severe adverse events, belantamab mafodotin is an "off-the-shelf" drug that can be administered in an outpatient setting. Many belantamab mafodotin-based combinations are under evaluation in Phase I, II, and III clinical trials either late or in early RRMM patients. Ocular toxicity represents a peculiar side effect of belantamab mafodotin. This toxicity is generally manageable with adequate dose reductions or delays since most patients who developed keratopathy recovered on treatment and discontinued ADC are rare. Here, we described the most recent clinical data of belantamab mafodotin and discussed the possible leading role of this intriguing agent in the near future of MM treatment
Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments
No full text: Immunotherapy is changing the paradigm of multiple myeloma (MM) management and daratumumab is the first-in-class human monoclonal antibody targeting CD38 approved for the treatment of this malignancy. Daratumumab exerts anti-myeloma activity by different mechanisms of action as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), direct apoptosis, and immunomodulation. After GEN501 and SIRIUS trials showed efficacy of daratumumab monotherapy in heavily pretreated relapsed-refractory multiple myeloma (RRMM), in patients with at least two previous line of therapy, two phase III trials demonstrated superior overall response rate (ORR) and progression free survival (PFS) using triplets daratumumab-bortezomib-dexamethasone (DVd) vs Vd (CASTOR) or daratumumab-lenalidomide-dexamethasone (DRd) vs Rd (POLLUX) in relapsed-refractory MM patients; so these combinations have been approved and introduced in clinical practice. The ongoing phase III CANDOR is evaluating the triplet daratumumab-carfilzomib-dexamethasone (DKd) vs Kd whereas phase III APOLLO trial is exploring daratumumab-pomalidomide-dexamethasone (DPd) vs PD. Many other trials exploring daratumumab combinations in relapsed-refractory MM are ongoing, and they will provide other interesting results. In newly diagnosed transplant-eligible patients, phase III CASSIOPEIA trial found the combination daratumumab-bortezomib-thalidomide-dexamethasone (Dara-VTd) significantly improves stringent Complete Response (sCR) rate and PFS compared with VTD, whereas in the phase II GRIFFIN study, comparing daratumumab-bortezomib-lenalidomide-dexamethasone (Dara-VRD) vs VRD, sCR rate was significantly higher using quadruplet combination. Many studies are evaluating daratumumab in consolidation and maintenance therapy after autologous stem cell transplantation (ASCT). As regard patients ineligible for ASCT, a great efficacy of daratumumab-containing combinations was reported by the phase III trials ALCYONE and MAIA, exploring daratumumab-bortezomib-melphalan-prednisone (DVMP) vs VMP and daratumumab-lenalidomide-dexamethasone (DRd) vs Rd, respectively. These studies provided results never seen before in this setting. The aim of this paper is to critically review the results obtained with regimens containing daratumumab both in relapsed-refractory and in newly diagnosed MM
Bendamustine for the treatment of multiple myeloma in first-line and relapsed-refractory settings: a review of clinical trial data
Full text linkMultiple myeloma (MM) is a hematologic malignancy characterized by abnormal growth and/or dysregulation of plasma cells leading to the build-up of malignant plasma cells in the bone marrow and increased production of monoclonal immunoglobulins. Treatment modalities for MM include autologous stem cell transplant (ASCT), chemotherapy with conventional and immunomodulatory agents, radiation therapy and adjunct therapies. Bendamustine is a synthetic chemotherapeutic agent combining the alkylating properties of a mustard group with the activities of a benzimidazole ring, giving it a unique alkylating activity compared with other alkylating agents. Bendamustine has proven activity in both newly diagnosed and relapsed-refractory MM. Bendamustine has also demonstrated activity in MM after relapse from ASCT, and has recently been used successfully as a conditioning regimen for ASCT in combination with melphalan. Bendamustine is generally well tolerated, with the majority of adverse events being due to bone marrow suppression. Extramedullary toxicity is infrequent and usually mild
AL amyloidosis: an overview on diagnosis, staging system, and treatment
Full text linkSystemic light-chain (AL) amyloidosis is a monoclonal plasma cell disease characterized by the deposition of amyloidogenic monoclonal light-chain fragments in organs, causing their dysfunction. Clinical manifestations could be very aspecific, but the most frequent ones are proteinuria with or without renal failure or heart failure, with the kidney and the heart being the first two involved organs. Histological diagnosis with Congo red staining is the gold standard, but typing the amyloid with immunohistochemistry or mass spectrometry of the Congo red positive tissue is necessary to establish if an AL or ATTR amyloidosis could be diagnosed. Staging AL amyloidosis before treatment could help physicians to prognosticate the disease. Recently, staging systems were set separately for different involved organs, using biomarkers. Autologous stem cell transplant after a daratumumab-based induction treatment is the cornerstone of therapy in younger and fit patients, with the goal of reaching a deep and rapid disease hematological and organ response. Novel therapies, borrowed from a therapeutical model of multiple myeloma, are studied to optimize AL amyloidosis outcomes. In this review, we make an overview of diagnostic procedures, staging system, and therapies of AL amyloidosis
NOVELTIES ON MULTIPLE MYELOMA FROM THE MAIN 2024 HEMATOLOGY CONFERENCES
Full text linkDespite the introduction of several therapies in recent years, multiple myeloma (MM) remains a hematologic malignancy difficult to treat due to its extreme inter- and intra-patient heterogeneity. However, at the 2024 major international conferences, very significant data have emerged on new approaches that can improve outcomes even in high-risk or very advanced diseases. Up-front quadruplet combinations, including anti-CD38 monoclonal antibodies, proved to be the best therapy in terms of depth of response and long-term efficacy in both transplant-eligible and not-eligible patients with MRD assessment that could play a key role in determining the duration of therapy, avoiding unnecessary overtreatment. However, quadruplets also fail to overcome the negative prognostic value of high-risk cytogenetics or circulating tumour cells; therefore, in patients with these features, alternative approaches will have to be evaluated. Moreover, considering that not all patients, particularly older and frail ones, will be able to undergo such therapies, it will be necessary to refine the ability to identify the most appropriate therapy for each patient. Bispecific antibodies and CAR-T cells represent the new frontier in the treatment of advanced MM. However, they have shown even more efficacy with less toxicity in early relapses and functional high-risk patients. In the upfront setting, the results obtained with the inclusion of novel immunotherapies are extremely promising. In relapsed/refractory MM patients, agents such as belantamab mafodotin and CELMoDs, in combination with proteasome inhibitors or immunomodulatory agents, may represent another valid option
Developments in consolidation and maintenance strategies in post-remission multiple myeloma
No full text: Introduction: Multiple Myeloma (MM) is a very heterogeneous clonal plasma cell hematological malignancy for which new therapies and transplantation effectively improve Progression-free survival (PFS) and overall survival (OS). Maintenance seems to have made a significant contribution in achieving these advances, whereas the real role of consolidation is still controversial. Despite lenalidomide having been approved as maintenance therapy after autologous stem cell transplantation (ASCT), the optimal maintenance agent, drug combinations, schedules, and duration are still under investigation.Areas covered: This review summarizes data regarding maintenance and consolidation therapies for transplant-eligible patients, updating on the ongoing developments in this area. Papers published on PubMed and abstracts presented at the ASCO, ASH, and EHA meetings up to December 2019 were used.Expert opinion: The available studies demonstrate that maintenance therapy is very effective although results from ongoing clinical trials suggest that disease features and minimal residual disease (MRD) status may optimize the selection of agents, schedule, and duration of maintenance therapy. Consolidation with last-generation drugs seems to be more effective and it could replace transplantation in some subgroups of patients
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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