Mechanisms of Resistance to Monoclonal Antibodies (mAbs) in Lymphoid Malignancies
AbstractPurpose of ReviewPassive immunotherapy with therapeutic monoclonal antibodies (mAbs) has revolutionized the treatment of cancer, especially hematological malignancies over the last 20  years. While use of mAbs has improved outcomes, development of resistance is inevitable in most cases, hindering the long-term survival of cancer patients. This review focuses on the available data on mechanisms of resistance to rituximab and includes some additional information for other mAbs cur rently in use in hematological malignancies.Recent FindingsMechanisms of resistance have been identified that target all described me...
Source: Current Hematologic Malignancy Reports - September 26, 2019 Category: Hematology Source Type: research

Venetoclax for the Treatment of Chronic Lymphocytic Leukemia
AbstractPurpose of this ReviewThis review summarizes the role of BCL-2 in the pathogenesis of CLL, and the clinical data evaluating safety and efficacy of venetoclax, in treatment of patients with CLL, in the context of other available targeted agents.Recent FindingsVenetoclax, alone or in combination with other targeted agents results in high rate of durable responses and undetectable measurable residual disease. Venetoclax maintains activity across all clinical and biologic subgroups, including those with high risk disease, including CLL with chromosome 17p deletion. TLS risk can be mitigated with risk stratification and...
Source: Current Hematologic Malignancy Reports - September 11, 2019 Category: Hematology Source Type: research

Chromatin-Remodeled State in Lymphoma
AbstractPurpose of ReviewEmerging evidence has shown that epigenetic derangements might drive and promote tumorigenesis in various types of malignancies and is prevalent in both B cell and T cell lymphomas. The purpose of this review is to explain how the epigenetic derangements result in a chromatin-remodeled state in lymphoma and contribute to the biology and clinical features of these tumors.Recent FindingsStudies have explored on the functional role of epigenetic derangements in chromatin remodeling and lymphomagenesis. For example, the haploinsufficiency of CREBBP facilitates malignant transformation in mice and direc...
Source: Current Hematologic Malignancy Reports - September 6, 2019 Category: Hematology Source Type: research

Molecular Mechanisms of Resistance to Tyrosine Kinase Inhibitors
AbstractPurpose of ReviewChronic myeloid leukemia (CML) patients with constitutive activity of BCR-ABL1 oncoprotein frequently derive significant clinical benefits from tyrosine kinase inhibitors (TKIs). Point mutations in the ABL1 kinase domain (KD) are an important mechanism of TKI resistance in CML. In this review, we present molecular mechanisms of TKI resistance paying particular attention to drug resistance which allows for a survival advantage in CML.Recent FindingsSensitive disease monitoring is a required standard of care for management of CML. Screening of these mutations fail to explain 20 –40% of resistan...
Source: Current Hematologic Malignancy Reports - August 28, 2019 Category: Hematology Source Type: research

Philadelphia-Negative Myeloproliferative Neoplasms: Laboratory Workup in the Era of Next-Generation Sequencing
AbstractPurpose of ReviewTo review the impact of next-generation sequencing (NGS) on laboratory approach of myeloproliferative neoplasms (MPNs).Recent FindingsNext-generation sequencing has provided valuable information on the mutational landscape of MPNs and has been used for various applications, including diagnosis, risk stratification, monitoring of residual disease or disease progression, and target therapy. Most commonly, targeted sequencing of a panel of genes that have been shown to be recurrently mutated in myeloid neoplasms is used. Although numerous studies have shown the benefit of using NGS in the routine clin...
Source: Current Hematologic Malignancy Reports - August 6, 2019 Category: Hematology Source Type: research

Novel Therapies in Myeloproliferative Neoplasms (MPN): Beyond JAK Inhibitors
AbstractPurpose of ReviewWith increased understanding of the pathobiology of myeloproliferative neoplasms (MPNs), multiple new agents are now being investigated. We aim to cover some of the current treatment options for MPNs and discuss new agents in development.Recent FindingsThe introduction of ruxolitinib improved the treatment of many patients with intermediate and higher risk myelofibrosis. However, ruxolitinib monotherapy does not benefit all patients, and not all patients can receive this therapy due to limiting cytopenias. The unraveling of new molecular abnormalities and cellular pathways led to the development of...
Source: Current Hematologic Malignancy Reports - August 1, 2019 Category: Hematology Source Type: research

Circulating Tumor Cells: State-of-the-art Update on Technologies and Clinical Applications
AbstractPurpose of ReviewCirculating tumor cells represent rare events in the peripheral blood of patients with cancer that can provide insight into tumor biology. CTC enumeration, isolation, and analysis represent liquid biopsy approaches whose role in the management of patients with cancer continues to evolve in the era of precision medicine. This review presents an overview of technologies central to studying CTCs.Recent FindingsTechnologies for CTC isolation can be divided into two categories: label-dependent and label-independent. Label-dependent techniques utilize biological properties such as cell surface proteins, ...
Source: Current Hematologic Malignancy Reports - July 30, 2019 Category: Hematology Source Type: research

The Role of PI3K Inhibition in Lymphoid Malignancies
AbstractPurpose of ReviewThe outcome of patients with lymphoid malignancies has markedly improved in recent years which is likely due to a combination of advances in supportive care, and therapeutic options. In this article, we will provide an overview over the role PI3-kinase signalling, one of the most important dysregulated pathways in cancer, and its successful inhibition in lymphoma.Recent FindingsPI3-kinase inhibitors have shown remarkable activity in an increasing subset of patients with non-Hodgkin lymphomas. The first drug to be approved was idelalisib for patients with relapsed/refractory follicular lymphoma and ...
Source: Current Hematologic Malignancy Reports - July 29, 2019 Category: Hematology Source Type: research

Acute Myeloid Leukemia: from Mutation Profiling to Treatment Decisions
AbstractPurpose of ReviewAwareness of the molecular landscape of AML has improved AML care over the last 5  years. This review summarizes updates regarding the diagnostic and therapeutic relevance of key mutations in AML.Recent FindingsMolecular mutations in genes including NPM1, CEBPA, FLT3, IDH1/2, TP53, RUNX1, and ASXL1 provide important prognostic and/or therapeutic information in AML, including best treatment strategies, transplant recommendations, and significance of MRD detection. Mutational analysis has led to the recognition of new entities including hereditary leukemia syndromes and clonal hematopoiesis of i...
Source: Current Hematologic Malignancy Reports - July 26, 2019 Category: Hematology Source Type: research

Liquid Biopsy by Next-Generation Sequencing: a Multimodality Test for Management of Cancer
AbstractPurpose of ReviewWhile liquid biopsy is still relatively a new concept, the advent of next-generation sequencing (NGS) technologies has recently generated a revolution in the field and will be the focus of this review.Recent FindingsCirculating tumor DNA (ctDNA) derives from tumor cells and provides information about the genetic alterations of tumors. However, ctDNA concentration in plasma can be below the level of detection by conventional methods; therefore, screening for actionable genetic information is challenging. Clinical trials exploring targeted and untargeted sequencing to improve the outcomes of ctDNA de...
Source: Current Hematologic Malignancy Reports - July 25, 2019 Category: Hematology Source Type: research

Immunohistochemistry Innovations for Diagnosis and Tissue-Based Biomarker Detection
AbstractPurpose of ReviewImmunohistochemistry is an integral technique for tissue-based diagnostics and biomarker detection with broad worldwide adoption. Advances in core chemistries, antibody design, and automation have ushered unprecedented sensitivity, specificity, and reproducibility in immunohistochemistry assays. As a result, clinical immunohistochemistry assays that utilize dual-color approaches and mutation-specific antibodies provide novel tools in clinical diagnostics that until recently were in the realm of investigational research. This review provides an overview of innovations in clinical immunohistochemistr...
Source: Current Hematologic Malignancy Reports - July 23, 2019 Category: Hematology Source Type: research

Multi-Specific CAR Targeting to Prevent Antigen Escape
AbstractPurpose of ReviewChimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable remission induction rates for relapsed/refractory B cell malignancies. However, loss of the CAR-targeted antigen, known as antigen escape, accounts for a substantial percentage of relapses following CAR therapy and is a major barrier to durable remission. Here, we discuss mechanisms for antigen escape and strategies to prevent this pattern of relapse, including the use of multi-specific CARs, which recognize and target multiple tumor-associated antigens simultaneously.Recent FindingsPreclinical and early clinical trial data ...
Source: Current Hematologic Malignancy Reports - July 22, 2019 Category: Hematology Source Type: research

IMiDs New and Old
AbstractPurpose of ReviewIMiDs are a class of biologic agents with immunomodulatory, anti-angiogenic, and direct anti-cancer activities. This review summarizes current data on clinical development and application of IMiDs in non-Hodgkin lymphoma (NHL) subtypes, focusing primarily on lenalidomide, with additional discussion on managing common side effects.Recent FindingsImproved upon the prototype thalidomide, the second-generation compound lenalidomide has enhanced immunological and anti-cancer properties with fewer side effects, while next-generation small molecule cereblon/E3 ubiquitin ligase modulator CC-122 is in early...
Source: Current Hematologic Malignancy Reports - July 13, 2019 Category: Hematology Source Type: research

Overcoming Challenges in Process Development of Cellular Therapies
AbstractPurpose of the ReviewCellular therapy using chimeric antigen receptor (CAR) T cells as a treatment option for patients with lymphoma and leukemia has proven to be remarkably efficacious. This success has sparked the development of new cellular therapy products for numerous indications. Similar to pharmaceutical products, challenges exist at nearly every stage of process development; however, the unique nature of a cellular therapy product can present exceptional challenges that are just beginning to emerge. The purpose of this review is to explore some of the most common challenges experienced during the early phas...
Source: Current Hematologic Malignancy Reports - July 6, 2019 Category: Hematology Source Type: research

Front-Line Treatment of High Grade B Cell Non-Hodgkin Lymphoma
AbstractPurpose of ReviewRituximab-based chemoimmunotherapy has resulted in a marked improvement in the survival of diffuse large B cell lymphoma (DLBCL). We reflect upon the history front-line (1L) therapy and highlight advances in management.Recent FindingsSince the introduction of R-CHOP, the majority of randomized studies in the front-line treatment of DLBCL have failed to show a benefit. Such studies have involved treatment intensification, adding novel agents to the R-CHOP backbone and targeting such novel agents to biologically defined subgroups. R-CHOP therefore remains standard-of-care for most but new insights in...
Source: Current Hematologic Malignancy Reports - June 29, 2019 Category: Hematology Source Type: research

Towards Automated Manufacturing for Cell Therapies
AbstractPurpose of ReviewMany cell therapy products are beginning to reach the commercial finish line and a rapidly escalating pipeline of products are in clinical development. The need to develop manufacturing capability that will support a successful commercial business model has become a top priority as many cell therapy developers look to secure long-term visions to enable both funding and treatment success.Recent FindingsManufacturing automation is both highly compelling and very challenging at the same time as a key tactic to address quality, cost of goods, scale, and sustainability that are fundamental drivers for c...
Source: Current Hematologic Malignancy Reports - June 28, 2019 Category: Hematology Source Type: research

Induced Pluripotent Stem Cell (iPSC) –Derived Lymphocytes for Adoptive Cell Immunotherapy: Recent Advances and Challenges
AbstractPurpose of ReviewIn the rapidly developing field of adoptive cell immunotherapy, there is urgent need for discoveries that would improve outcomes, extend the applicability, and reduce the costs. Induced pluripotent stem cells (iPSC) can be a source of broadly applicable cellular immunotherapeutics, which have been manufactured, validated, and banked in advance, and can be applied across HLA barriers. Here, we discuss the recent advances and challenges in the generation of iPSC-derived cellular products for cancer therapy.Recent FindingsiPSCs can be differentiated to functional tumor-specific T and NK cells in vitro...
Source: Current Hematologic Malignancy Reports - June 26, 2019 Category: Hematology Source Type: research

Targeting Translation of mRNA as a Therapeutic Strategy in Cancer
AbstractPurpose of ReviewTo highlight recent results in targeting mRNA translation and discuss the results and prospects of translation inhibitors in cancer therapy.Recent FindingsUntil recently, inhibitors of mRNA translation have been thought to likely lack a therapeutic window. In 2012, the Food and Drug Administration (FDA) approved omacetaxine mepesuccinate (homoharringtonine) for the treatment of adults with chronic myelogenous leukemia (CML) who are resistant to at least two tyrosine kinase inhibitors. Since then, a few drugs, notably tomivosertib (eFT-508), selinexor (KPT-330), and ribavirin, have entered clinical ...
Source: Current Hematologic Malignancy Reports - June 24, 2019 Category: Hematology Source Type: research

Pathogen-Specific T Cells Beyond CMV, EBV and Adenovirus
AbstractPurpose of ReviewInfectious diseases contribute significantly to morbidity and mortality in recipients of allogeneic haematopoietic stem cell transplantation (aHSCT), particularly in the era of highly immunosuppressive transplant regimens and alternate donor transplants. Delayed cellular immune recovery is a major mechanism for the increased risk in these patients. Adoptive cell therapy with ex vivo manipulated pathogen-specific T cells (PSTs) is increasingly taking its place as a treatment strategy using donor-derived or third party –banked cells.Recent FindingsThe majority of clinical trial data in the form...
Source: Current Hematologic Malignancy Reports - June 21, 2019 Category: Hematology Source Type: research

Considerations for the Treatment of Diffuse Large B Cell Lymphoma in the Elderly
AbstractPurpose of ReviewDiffuse large B cell lymphoma (DLBCL) is a curable and common malignancy in elderly population. Elderly patients, especially those 80 and older, have poor outcomes compared with those
Source: Current Hematologic Malignancy Reports - June 21, 2019 Category: Hematology Source Type: research

The Rationale for Immunotherapy in Myeloproliferative Neoplasms
AbstractPurpose of ReviewThe classic, chronic Philadelphia chromosome negative myeloproliferative neoplasms (MPN) —essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF)—are clonal malignancies of hematopoietic stem cells and are associated with myeloproliferation, organomegaly, and constitutional symptoms. Expanding knowledge that chronic inflammation and a dysregulated immune syste m are central to the pathogenesis and progression of MPNs serves as a driving force for the development of agents affecting the immune system as therapy for MPN. This review describes the rationale and poten...
Source: Current Hematologic Malignancy Reports - June 21, 2019 Category: Hematology Source Type: research

Mantle Cell Lymphoma: Which Patients Should We Transplant?
AbstractPurpose of ReviewMantle cell lymphoma is a CD5+ non-Hodgkin lymphoma associated with suboptimal outcome. Young, fit patients are generally offered intensive induction followed by autologous hematopoietic cell transplantation (AHCT) in first remission. Some patients may not benefit from this strategy.Recent FindingsRecent studies have investigated the role of AHCT in the modern era. First, an analysis of the National Cancer Database demonstrated improved progression-free survival (PFS) for consolidative AHCT. Second, a multi-center study associated consolidative AHCT with improved PFS even after propensity-weighted ...
Source: Current Hematologic Malignancy Reports - June 19, 2019 Category: Hematology Source Type: research

Emerging Role of Integrative Medicine in Hematologic Malignancies: a Literature Review and Update on Current Trends in Complementary Medical Practices in Hematologic Cancers
AbstractPurpose of ReviewThis review discusses the emerging role of integrative hematology. It reinforces the growing interest of CAM among patients, and the importance of provider knowledge and participation in discussions with patients about the subject. The main question asked in this review, “Is there evidence for the use of integrative medicine practices in the field of malignant hematology?” is answered by examining current research and providing relevant summaries.Recent FindingsData suggests that practices such as meditative movement, exercise, nutrition and supplements and touch therapy can be used for...
Source: Current Hematologic Malignancy Reports - June 18, 2019 Category: Hematology Source Type: research

Exploring a Future for PI3K Inhibitors in Chronic Lymphocytic Leukemia
AbstractPurpose of ReviewTreatment for chronic lymphocytic leukemia has changed substantially in the past decade with an increasing shift towards use of targeted therapies, in particular agents targeting the B cell receptor pathway. Inhibition of PI3K, downstream of the B cell receptor pathway, represents an active therapeutic strategy in CLL. Here, we explore the relevance of PI3K inhibition in CLL, examine efficacy and toxicity of approved PI3K inhibitors in CLL, examine barriers to use of PI3K inhibitors, and explore strategies to optimize use of PI3K inhibitors in CLL.Recent FindingsCurrent generation PI3K inhibitors a...
Source: Current Hematologic Malignancy Reports - June 15, 2019 Category: Hematology Source Type: research

Activin Receptor II Ligand Traps: New Treatment Paradigm for Low-Risk MDS
AbstractPurpose of ReviewAlleviating cytopenias, namely anemia, is the main goal of therapy in lower-risk myelodysplastic syndromes (MDS). Current available treatment options remain limited. We review the role of TGF-B pathway in MDS, the current available data on luspatercept and sotatercept development.Recent FindingsTGF-B pathway is overactivated in MDS contributing to observed myelosuppression. SMADs, the downstream proteins of TGF-B pathway, are upregulated. GDF-11 is a negative regulator of terminal erythroid differentiation and an activin receptor ligand. Sotatercept and luspatercept are fusion ligand trap novel age...
Source: Current Hematologic Malignancy Reports - June 15, 2019 Category: Hematology Source Type: research

Is There a Role for Dose Modification of TKI Therapy in CML?
AbstractPurpose of ReviewFor patients with chronic phase chronic myeloid leukemia (CP-CML), there is an increasing focus on personalization of therapy with dose modifications of tyrosine kinase inhibitors (TKIs) to reduce side effects and maintain efficacy. Dose reductions are also being considered in clinical trials prior to treatment-free remission (TFR) attempts.Recent FindingsRecent retrospective analyses of large clinical trials show that dose modification/reduction is safe. Efficacy is generally maintained and side effects are improved. Clinical trials such as DESTINY have demonstrated that dose reduction is safe for...
Source: Current Hematologic Malignancy Reports - June 14, 2019 Category: Hematology Source Type: research

Tumor-Infiltrating Lymphocytes in the Checkpoint Inhibitor Era
AbstractPurpose of ReviewCheckpoint inhibitors block co-inhibitory signals which serves to promote T cell activation/reinvigoration in the periphery and tumor microenvironment. A brief historical background as well as a summary of key observations related to the composition and prognostic value of tumor-infiltrating lymphocytes (TILs) is discussed.Recent FindingsSolid tumor patients that respond to checkpoint inhibitors have greater CD8+ T cell densities (at the tumor margin) associated with a gene inflammation signature and high tumor mutational burden. The precise specificity of effector (CD8+ T cell) TIL remains poorly ...
Source: Current Hematologic Malignancy Reports - June 11, 2019 Category: Hematology Source Type: research

Key Role of Inflammation in Myeloproliferative Neoplasms: Instigator of Disease Initiation, Progression. and Symptoms
AbstractPurpose of ReviewChronic inflammation is a characteristic feature of myeloproliferative neoplasm (MPN) and impacts many aspects of the disease including initiation, progression, and symptomatology.Recent FindingsThe chronic inflammatory state of MPN results from disruption of immune signaling pathways leading to overproduction of inflammatory cytokines by both the neoplastic clones and bystander immune cells. This chronic inflammation may allow for the neoplastic clone to gain a selective advantage. The symptomatic burden felt by MPN patients may be a result of the chronic inflammation associated with MPN, as sever...
Source: Current Hematologic Malignancy Reports - May 22, 2019 Category: Hematology Source Type: research

Chronic Myelomonocytic Leukemia: 2018 Update to Prognosis and Treatment
AbstractPurpose of ReviewChronic myelomonocytic leukemia (CMML) is a rare and often aggressive myeloid malignancy. Historically, prognostic markers and therapeutic paradigms have been applied from myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPNs). Interest has increased recently in developing tailored approaches for the MDS/MPNoverlap syndrome of CMML.Recent FindingsMultiple prognostic scores have been validated specifically for CMML in the past 5  years. These incorporate somatic mutations, withASXL1 mutations repeatedly correlating with poor prognosis. Accurate prognostication can guide treatmen...
Source: Current Hematologic Malignancy Reports - May 15, 2019 Category: Hematology Source Type: research

Integrative Approaches to Managing Myeloproliferative Neoplasms: the Role of Nutrition, Exercise, and Psychological Interventions
AbstractPurpose of ReviewMyeloproliferative neoplasms (MPNs) have a high symptom burden that affects functional status, emotional well-being, and quality of life for patients. Symptom control continues to be a challenging therapeutic goal despite available pharmacologic interventions. The goal of this review is to detail recent efforts that have focused on non-pharmacologic interventions, such as wholistic or integrative medicine, as an adjunctive method to alter symptom burden in this population.Recent FindingsWe discuss the ongoing physical, nutritional, and psychological interventional efforts which represent promising ...
Source: Current Hematologic Malignancy Reports - May 15, 2019 Category: Hematology Source Type: research

Trends in Clinical Benefits and Costs of Novel Therapeutics in AML: at What Price Does Progress Come?
AbstractPurpose of ReviewSince 2017, eight novel agents have been approved for the treatment of acute myeloid leukemia (AML) in the USA. Here, we review the clinical benefits and costs associated with these drugs.Recent FindingsFor some of the newly-approved drugs, clinical benefit has been documented in randomized trials. Others received accelerated approval based on surrogate endpoints in early phase trials. All, however, carry significant costs and toxicities. Cost-effectiveness analyses are so far only available for midostaurin, CPX-351, and gemtuzumab ozogamicin.SummaryRecently approved drugs for AML have varying leve...
Source: Current Hematologic Malignancy Reports - May 11, 2019 Category: Hematology Source Type: research

Expert Panel Consensus Statement for Proper Evaluation of First Relapse in Multiple Myeloma
AbstractPurpose of ReviewA working group of six expert physicians convened to assess the spectrum of multiple myeloma relapse presentations, discussed the features that can define the disease as aggressive and not aggressive, and established whether this information could help in selecting treatment together with the characteristics of disease and of patients and type of prior therapy.Recent FindingsThe working group agreed that relapse should be distinguished between biochemical and clinical according to IMWG. Moreover, the expert panel defined “aggressive disease” as a clinical condition that requires therapy...
Source: Current Hematologic Malignancy Reports - May 10, 2019 Category: Hematology Source Type: research

Disparities in Survival and Health Outcomes in Childhood Leukemia
AbstractPurpose of ReviewThe aim of this review is to summarize the current literature on pediatric leukemia disparities with attention to not only racial and ethnic disparities, but also socioeconomic disparities. We focus on disparities in survival as well as other health-related outcomes, including end-of-life care and late effects.Recent FindingsWhile progress has been made in decreasing some disparities, most notably in pediatric acute lymphoblastic leukemia, disparities along many axes persist. Proposed etiologies include differences in the genomic alterations of the leukemia itself to differences in access to care t...
Source: Current Hematologic Malignancy Reports - May 9, 2019 Category: Hematology Source Type: research

Relevance of Prognostic Factors in the Era of Targeted Therapies in CLL
AbstractPurpose of ReviewClinicians continue to utilize prognostic biomarkers, such as expression of CD38 and ZAP-70,IGHV mutational status, cytogenetic abnormalities, and genomic aberrations inTP53, to guide prognosis and treatment of patients with CLL. These biomarkers have been validated with standard chemoimmunotherapy. Here, we discuss whether these biomarkers maintain their prognostic significance in the era of targeted therapy.Recent FindingsMultiple phase 3 clinical trials have now proven improved efficacy of targeted therapy over traditional chemoimmunotherapy. We now have ample prospective data using targeted the...
Source: Current Hematologic Malignancy Reports - May 2, 2019 Category: Hematology Source Type: research

Next-Generation Sequencing in Myeloproliferative Neoplasms: Is This Indicated in All Patients?
AbstractPurpose of reviewTo discuss the impact that next-generation sequencing has had on myeloproliferative neoplasm prognosis and treatment response.Recent findingsExtended genetic testing has led to a more comprehensive understanding of the mutational landscape in the myeloproliferative neoplasms. More refined prognostic models that predict disease course have therefore been developed. In myelofibrosis, this has led to a more nuanced prognostic assessment which is a necessary tool for the identification of potential transplant patients. The extended molecular profile may also help set expectations for ruxolitinib respon...
Source: Current Hematologic Malignancy Reports - April 30, 2019 Category: Hematology Source Type: research

Correction to: Autologous Haematopoietic Stem Cell Transplantation in Multiple Sclerosis: a Review of Current Literature and Future Directions for Transplant Haematologists and Oncologists
Modifications have been made to the 5th paragraph of the section"Efficacy", and in Table 3; Additional authors ’ information has also been added as an article note in the front matter. (Source: Current Hematologic Malignancy Reports)
Source: Current Hematologic Malignancy Reports - April 27, 2019 Category: Hematology Source Type: research

Targeting BTK in CLL: Beyond Ibrutinib
AbstractPurpose of ReviewWhile the Bruton ’s tyrosine kinase inhibitor (BTKi) ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia (CLL), current limitations include off-target toxicities and the development of resistance. In this review, we summarize the emerging data for alternative BTKi.Recent FindingsSecond-generation BTKi include acalabrutinib, zanubrutinib, and tirabrutinib which offer greater BTK selectivity. While these agents may limit off-target toxicity, they do not overcome common mechanisms of ibrutinib resistance. Reversible BTKi including vecabrutinib and LOXO-305 inhibit BTK in t...
Source: Current Hematologic Malignancy Reports - April 27, 2019 Category: Hematology Source Type: research

Relapsed T Cell ALL: Current Approaches and New Directions
This article summarizes current approaches and promising emerging strategies for the treatment of relapsed T-ALL.Recent FindingsAlthough nelarabine is the only agent approved specifically for T-ALL, recent studies have identified a variety of genetic alterations and signaling pathways that are critical in its pathogenesis. Based on these findings, a number of small-molecule inhibitors and other targeted therapies are being studied for relapsed T-ALL, including gamma-secretase inhibitors, BCL-2 inhibitors, cyclin-dependent kinase inhibitors, and mTOR inhibitors. In addition, pre-clinical studies of chimeric antigen receptor...
Source: Current Hematologic Malignancy Reports - March 18, 2019 Category: Hematology Source Type: research

Recent Advances in Adult Acute Lymphoblastic Leukemia
This article reviews the recent advances in the pathophysiology and management of acute lymphoblastic leukemia (ALL) in adults.Recent FindingsAddition of rituximab to standard chemotherapy improves survival in the frontline treatment of B cell ALL, and measurable residual disease (MRD) is the most important prognostic factor. Tyrosine kinase inhibitors (TKI), particularly ponatinib, in combination with Hyper-CVAD significantly improve outcomes in Ph + ALL challenging the benefit of allogeneic stem cell transplant in first line for these patients. Blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor (CAR) T ce...
Source: Current Hematologic Malignancy Reports - March 16, 2019 Category: Hematology Source Type: research

Development and Significance of Mouse Models in Lymphoma Research
In conclusion, the refinement and advancement of available mouse models in lymphoma significantly minimize the therapeutic translational failures in patients. (Source: Current Hematologic Malignancy Reports)
Source: Current Hematologic Malignancy Reports - March 8, 2019 Category: Hematology Source Type: research

Autologous Haematopoietic Stem Cell Transplantation in Multiple Sclerosis: a Review of Current Literature and Future Directions for Transplant Haematologists and Oncologists
AbstractPurpose of ReviewWe summarise the current development of autologous haematopoietic stem cell transplantation (AHSCT) in treating multiple sclerosis (MS) and discuss future directions for the general neurologist, transplant haematologist and oncologist.Recent FindingsAHSCT was initially performed to treat MS over 20  years ago. Over recent years, the evidence base has grown, especially in relapsing-remitting MS (RRMS), with significant improvements in safety and efficacy through better patient selection, choice of transplant technique and increase in centre experience.SummaryAHSCT is now a treatment option in v...
Source: Current Hematologic Malignancy Reports - March 4, 2019 Category: Hematology Source Type: research

Challenges and Strategies in the Management of Multiple Myeloma in the Elderly Population
AbstractPurpose of ReviewApproximately one half of the patient-population in multiple myeloma (MM) is>  70 years at diagnosis. Despite notable strides in the management and improved survival, MM remains incurable, with an increasing proportion of elderly patients comprising the relapsed-refractory cohort.Recent FindingsThe arbitrary age cutoff at 65  years to define the elderly patient-population has evolved to a more nuanced categorization, incorporating a comprehensive assessment for determining frailty prior to commencing treatment. This step is critical in determining the therapy-intensity, includin...
Source: Current Hematologic Malignancy Reports - February 28, 2019 Category: Hematology Source Type: research

The Emerging Role of Liquid Biopsies in Lymphoproliferative Disorders
AbstractPurpose of the ReviewLymphomas represent clinically and molecularly heterogeneous diseases with variable presentations, treatment algorithms, and outcomes. As treatment options continue to expand, more sophisticated prognostic and predictive biomarkers are needed to guide personalized treatment approaches.Recent FindingsLiquid biopsies, in which the sequencing of circulating tumor DNA (ctDNA) in peripheral blood serves as a surrogate for a tumor biopsy, are now being studied across cancer subtypes, including in lymphoid malignancies. Recent studies have demonstrated the potential of these techniques to improve prog...
Source: Current Hematologic Malignancy Reports - February 27, 2019 Category: Hematology Source Type: research

Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoblastic Leukemia
AbstractPurpose of ReviewThe remarkable improvement in the prognosis of children with acute lymphoblastic leukemia (ALL) has been mainly achieved through the administration of risk-adapted therapy, including allogeneic hematopoietic stem cell transplantation (HSCT). This paper reviews the current indications to HSCT in ALL children, as well as the type of donor and conditioning regimens commonly used. Finally, it will focus on future challenges in immunotherapy.Recent FindingsAs our comprehension of disease-specific risk factors improves, indications to HSCT continue to evolve. Future studies will answer the year-old quest...
Source: Current Hematologic Malignancy Reports - February 26, 2019 Category: Hematology Source Type: research

Solitary Plasmacytoma: a Review of Diagnosis and Management
AbstractPurpose of ReviewSolitary plasmacytoma is a rare plasma cell dyscrasia, classified as solitary bone plasmacytoma or solitary extramedullary plasmacytoma. These entities are diagnosed by demonstrating infiltration of a monoclonal plasma cell population in a single bone lesion or presence of plasma cells involving a soft tissue mass, respectively. Both diseases represent a single localized process without significant plasma cell infiltration into the bone marrow or evidence of end organ damage. Clinically, it is important to classify plasmacytoma as having completely undetectable bone marrow involvement versus minima...
Source: Current Hematologic Malignancy Reports - February 20, 2019 Category: Hematology Source Type: research

Determination of Minimal Residual Disease in Multiple Myeloma: Does It Matter?
AbstractPurpose of ReviewThe ability to detect minimal residual disease (MRD) in myeloma has improved due to advances in flow cytometry and sequencing methodologies. Here, we evaluate recent clinical trial data and explore the current and future roles of MRD assessment in the context of clinical trial design and clinical practice.Recent FindingsA review of recent phase III studies reveals that achievement of MRD negativity is associated with improved progression-free survival (PFS) and/or overall survival (OS). Treatment arms that are more effective from a PFS or overall response rate perspective are also associated with s...
Source: Current Hematologic Malignancy Reports - January 22, 2019 Category: Hematology Source Type: research

Immunotherapeutic Approaches for Multiple Myeloma: Where Are We Now?
AbstractPurpose of ReviewThe treatment landscape for multiple myeloma has evolved rapidly with the availability of multiple new drugs; however, although patient survival has improved, the disease remains incurable. Multiple myeloma is characterized by the unregulated growth of malignant plasma cells accompanied by immune dysfunction as well as disrupted immune surveillance mechanisms. Here, we analyze clinical modalities, with a focus on monoclonal antibodies and adoptive cellular therapy that enhance patients ’ immune systems and overcome these defects.Recent FindingsEarly clinical trials with PD-1 inhibitors were p...
Source: Current Hematologic Malignancy Reports - January 21, 2019 Category: Hematology Source Type: research

Industry ’s Giant Leap Into Cellular Therapy: Catalyzing Chimeric Antigen Receptor T Cell (CAR-T) Immunotherapy
We describe the significant technological leap from bench to bedside that was achieved through a strong academic-industry collaboration between dedicated clinicians and researchers at the University of Pennsylvania, the Children ’s Hospital of Philadelphia, and Novartis to commercialize the chimeric antigen receptor T cell (CAR-T) therapy tisagenlecleucel (CTL019; Kymriah®; Novartis Pharma AG, Basel, Switzerland).Recent FindingsTisagenlecleucel was the first CAR-T therapy and the first gene therapy to receive US Food and Drug Administration approval in 2017, with an initial indication for pediatric and young adul...
Source: Current Hematologic Malignancy Reports - January 21, 2019 Category: Hematology Source Type: research

Should Overall Survival Remain an Endpoint for Multiple Myeloma Trials?
AbstractPurpose of ReviewWhile the traditional gold standard for demonstrating clinical benefit of a therapy has been to show prolongation of overall survival (OS), there are multiple factors which can hinder the use of OS as a primary endpoint in randomized clinical trials (RCTs). Here, we analyze recent myeloma RCTs and evaluate the issues relevant to current and future myeloma RCT design.Recent FindingsA review of recent phase III RCTs that led to approval of new agents/combinations reveals that none were designed with OS as the primary endpoint, but instead utilized time to progression (TTP) or progression-free surviva...
Source: Current Hematologic Malignancy Reports - January 19, 2019 Category: Hematology Source Type: research

Treatment-Free Remission in CML: the US Perspective
AbstractPurpose of ReviewChronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI) have near-normal life expectancy. However, lifelong TKI therapy is associated with reduced quality of life and significant economic burden. Currently, the management of CML is shifting from continuous TKI therapy towards the goal of TKI cessation which is discussed in this review.Recent FindingsSeveral studies in the last decade have demonstrated the feasibility and safety of TKI discontinuation in selected patients with CML who achieve deep and sustained molecular response with TKI. This has moved prime-time into...
Source: Current Hematologic Malignancy Reports - January 15, 2019 Category: Hematology Source Type: research