Current Hematologic Malignancy Reports最新文献

{"title":"Molecular Pathogenesis of Myeloproliferative Neoplasms.","authors":"Benjamin Rolles,&nbsp;Ann Mullally","doi":"10.1007/s11899-022-00685-1","DOIUrl":"https://doi.org/10.1007/s11899-022-00685-1","url":null,"abstract":"<p><strong>Purpose of review: </strong>Myeloproliferative neoplasms (MPNs) are chronic hematological malignancies characterized by increased proliferation of MPN stem and myeloid progenitor cells with or without bone marrow fibrosis that typically lead to increased peripheral blood cell counts. The genetic and cytogenetic alterations that initiate and drive the development of MPNs have largely been defined, and we summarize these here.</p><p><strong>Recent findings: </strong>In recent years, advances in understanding the pathogenesis of MPNs have defined a long-preclinical phase in JAK2-mutant MPN, identified genetic loci associated with MPN predisposition and uncovered mechanistic insights in CALR-mutant MPN. The integration of molecular genetics into prognostic risk models is well-established in myelofibrosis and ongoing studies are interrogating the prognostic implications of concomitant mutations in ET and PV. Despite all these advances, the field is deficient in clonally selective therapies to effectively target the MPN clone at any stage of disease, from pre-clinical to advanced. Although the biological understanding of the pathogenesis of MPNs has progressed quickly, substantial knowledge gaps remain, including in the molecular mechanisms underlying MPN progression and myelofibrotic transformation. An ongoing goal for the MPN field is to translate advances in biological understanding to improved treatments for patients.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9185985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Germline Predisposition to Therapy-Related Myeloid Neoplasms.","authors":"Anmol Baranwal,&nbsp;Christopher N Hahn,&nbsp;Mithun Vinod Shah,&nbsp;Devendra K Hiwase","doi":"10.1007/s11899-022-00676-2","DOIUrl":"https://doi.org/10.1007/s11899-022-00676-2","url":null,"abstract":"<p><strong>Purpose of review: </strong>Therapy-related myeloid neoplasms (t-MNs) are aggressive leukemias that develop following exposure to DNA-damaging agents. A subset of patients developing t-MN may have an inherited susceptibility to develop myeloid neoplasia. Herein, we review studies reporting t-MN and their association with a germline or inherited predisposition.</p><p><strong>Recent findings: </strong>Emerging evidence suggests that development of t-MN is the result of complex interactions including generation of somatic variants in hematopoietic stem cells and/or clonal selection pressure exerted by the DNA-damaging agents, and immune evasion on top of any inherited genetic susceptibility. Conventionally, alkylating agents, topoisomerase inhibitors, and radiation have been associated with t-MN. Recently, newer modalities including poly (ADP-ribose) polymerase inhibitors (PARPi) and peptide receptor radionucleotide therapy (PRRT) are associated with t-MN. At the same time, the role of pathogenic germline variants (PGVs) in genes such as BRCA1/2, BARD1, or TP53 on the risk of t-MN is being explored. Moreover, studies have shown that while cytotoxic therapy increases the risk of developing myeloid neoplasia, it may be exposing the vulnerability of an underlying germline predisposition. t-MN remains a disease with poor prognosis. Studies are needed to better define an individual's inherited neoplastic susceptibility which will help predict the risk of myeloid neoplasia in the future. Understanding the genes driving the inherited neoplastic susceptibility will lead to better patient- and cancer-specific management including choice of therapeutic regimen to prevent, or at least delay, development of myeloid neoplasia after treatment of a prior malignancy.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10615888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress and Challenges in Survivorship After Acute Myeloid Leukemia in Adults.","authors":"Ginna Granroth, Nandita Khera, Cecilia Arana Yi","doi":"10.1007/s11899-022-00680-6","DOIUrl":"10.1007/s11899-022-00680-6","url":null,"abstract":"<p><strong>Purpose of review: </strong>Acute myeloid leukemia (AML) survivors face unique challenges affecting long-term outcomes and quality of life. There is scant literature on the long-term impact of AML treatment in physical and mental health, disease recurrence, and financial burden in survivors.</p><p><strong>Recent findings: </strong>Fatigue, mental health concerns, infections, sexual dysfunction, and increase cancer recurrence occur after AML treatment. Chronic graft-versus-host disease (GVHD) and infections are common concerns in AML after hematopoietic stem cell transplantation (HCT). Survivorship guidelines encompass symptoms and complications but fail to provide an individualized care plan for AML survivors. Studies in patient-reported outcomes (PROs) and health-related quality of life (HRQoL) are sparse. Here we discuss the most common aspects pertaining to AML survivorship, late complications, care delivery, prevention of disease recurrence, and potential areas for implementation.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10615916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining Higher-Risk Chronic Myeloid Leukemia: Risk Scores, Genomic Landscape, and Prognostication.","authors":"Nur Hezrin Shahrin,&nbsp;Carol Wadham,&nbsp;Susan Branford","doi":"10.1007/s11899-022-00668-2","DOIUrl":"https://doi.org/10.1007/s11899-022-00668-2","url":null,"abstract":"<p><strong>Purpose of review: </strong>The chronic myeloid leukemia (CML) treatment success story is incomplete as some patients still fail therapy, leading to end-stage disease and death. Here we discuss recent research into CML incidence, the role of comorbidities on survival and detecting patients at risk of failing therapy.</p><p><strong>Recent findings: </strong>The incidence of CML has fallen markedly in high social-demographic index (SDI) regions of the world but there is disturbing evidence that this is not the case in low and low-middle SDI countries. Now that CML patients more frequently die from their co-morbid conditions than from CML the Adult Comorbidity Evaluation-27 score can assist in risk assessment at diagnosis. Non-adherence to therapy contributes greatly to treatment failure. A good doctor-patient relationship and social support promote good adherence, but patient age, gender, and financial burden have negative effects, suggesting avenues for intervention. Mutations in cancer-associated genes adversely affect outcome and their detection at diagnosis may guide therapeutic choice and offer non-BCR::ABL1 targeted therapies. A differential gene expression signature to assist risk detection is a highly sought-after diagnostic tool being actively researched on several fronts. Detecting patients at risk of failing therapy is being assisted by recent technological advances enabling highly sensitive genomic and expression analysis of insensitive cells. However, patient lifestyle, adherence to therapy, and comorbidities are critical risk factors that need to be addressed by interventions such as social and financial support.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10615877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Determinants of Return to Work as a Patient-Centered Outcome in Survivors of Hematopoietic Cell Transplantation.","authors":"Neel S Bhatt","doi":"10.1007/s11899-022-00678-0","DOIUrl":"https://doi.org/10.1007/s11899-022-00678-0","url":null,"abstract":"<p><strong>Purpose of review: </strong>Employment is an important indicator of health and functional recovery for hematopoietic cell transplantation (HCT) survivors and has significant social and economic impacts. Cancer survivors treated with conventional non-HCT therapy are known to be at a higher risk of unemployment or not returning to work after completion of therapy compared with the control population. However, the literature on return-to-work challenges among HCT survivors remains limited.</p><p><strong>Recent findings: </strong>Here we summarize the evidence on prevalence and determinants of return-to-work challenges among HCT survivors using previously published literature. Findings from previously published research show that return to work or unemployment is a major concern among HCT survivors, especially for allogeneic HCT recipients, and prior studies have identified several modifiable risk factors associated with it. Survivors' post-HCT employment status is significantly associated with quality of life, impacting physical, emotional, social, and financial aspects of their lives. We also highlight the gaps in current knowledge such as limited information on employment outcomes of childhood, adolescent, and young adult HCT survivors; work-related challenges among employed HCT survivors; consequences of work-related challenges; and interventions to improve return to work among HCT survivors. Findings highlighted in this review make a strong case of a multidisciplinary return-to-work support for HCT survivors to properly address their needs.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10613725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapy Resistance and Disease Progression in CML: Mechanistic Links and Therapeutic Strategies.","authors":"John Joson Ng,&nbsp;S Tiong Ong","doi":"10.1007/s11899-022-00679-z","DOIUrl":"https://doi.org/10.1007/s11899-022-00679-z","url":null,"abstract":"<p><strong>Purpose of review: </strong>Despite the adoption of tyrosine kinases inhibitors (TKIs) as molecular targeted therapy in chronic myeloid leukemia, some patients do not respond to treatment and even experience disease progression. This review aims to give a broad summary of advances in understanding of the mechanisms of therapy resistance, as well as management strategies that may overcome or prevent the emergence of drug resistance. Ultimately, the goal of therapy is the cure of CML, which will also require an increased understanding of the leukemia stem cell (LSC).</p><p><strong>Recent findings: </strong>Resistance to tyrosine kinase inhibitors stems from a range of possible causes. Mutations of the BCR-ABL1 fusion oncoprotein have been well-studied. Other causes range from cell-intrinsic factors, such as the inherent resistance of primitive stem cells to drug treatment, to mechanisms extrinsic to the leukemic compartment that help CML cells evade apoptosis. There exists heterogeneity in TKI response among different hematopoietic populations in CML. The abundances of these TKI-sensitive and TKI-insensitive populations differ from patient to patient and contribute to response heterogeneity. It is becoming clear that targeting the BCR-ABL1 kinase through TKIs is only one part of the equation, and TKI usage alone may not cure the majority of patients with CML. Considerable effort should be devoted to targeting the BCR-ABL1-independent mechanisms of resistance and persistence of CML LSCs.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10616405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Belantamab Mafodotin, Selinexor, and Melflufen in Multiple Myeloma.","authors":"Arleigh McCurdy,&nbsp;Alissa Visram","doi":"10.1007/s11899-022-00682-4","DOIUrl":"https://doi.org/10.1007/s11899-022-00682-4","url":null,"abstract":"<p><strong>Purpose of review: </strong>Multiple myeloma (MM) is a hematologic malignancy of plasma cells that remains incurable with currently available therapies including proteosome inhibitors, immunomodulators, monoclonal antibodies, corticosteroids, and alkylators, in addition to autologous stem cell transplantation in patients who are eligible. Novel therapeutics are therefore required to improve patient outcomes. The goal of this paper is to review the role of three new agents in the MM treatment landscape: belantamab mafodotin, selinexor, and melflufen.</p><p><strong>Recent findings: </strong>All three agents have demonstrated clinical activity in patients with MM. Belamaf is the first FDA-approved anti-BCMA targeted agent, showing single-agent response rates of 60% and higher response rates of 48-100% in combinations. The majority of patients treated with belamaf experience corneal toxicity which remains the main challenge with its use; however, fortunately, the vast majority of patients recover. Selinexor is also FDA approved for the treatment of relapsed MM, with single-agent response rates of 26% and combination rates of 48-65%. Gastrointestinal side effects are common with selinexor use, with roughly 65% of patients experiencing nausea, 50% anorexia, 35% vomiting, and 42% diarrhea, the majority of which are grades 1-2. Both agents have a plethora of ongoing clinical trials with data forthcoming on various combinations with standard backbone agents as well as additional novel treatments. While melflufen showed promising initial data showing single-agent response rates of about 30%, inferior survival outcomes in patients previously treated with ASCT in the phase 3 OCEAN study lead to early termination of the trial and subsequent removal from the US market. Belamaf, selinexor, and melflufen are active agents to treat myeloma. Belamaf and selinexor are current options for the treatment of relapsed multiple myeloma with improved response rates and durability when used in triplet combinations. The optimal timing of use and treatment combinations of both agents in the context of additional immunotherapeutics entering the MM landscape requires further study. Many prospective studies are in development and promise to afford further clarity in the near future.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9170605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric Germline Predisposition to Myeloid Neoplasms.","authors":"Christineil Thompson,&nbsp;Sydney Ariagno,&nbsp;Mira A Kohorst","doi":"10.1007/s11899-022-00681-5","DOIUrl":"https://doi.org/10.1007/s11899-022-00681-5","url":null,"abstract":"<p><strong>Purpose of review: </strong>Advances in the understanding of germline predisposition to pediatric cancers, particularly myeloid neoplasms, have increased rapidly over the last 20 years. Here, we highlight the most up-to-date knowledge regarding known pathogenic germline variants that contribute to the development of myeloid neoplasms in children.</p><p><strong>Recent findings: </strong>This discussion enumerates the most notable myeloid neoplasm-causing germline mutations. These mutations may be organized based on their molecular underpinnings-transcriptional control, splicing and signal transduction control, and a group of heterogeneous bone marrow failure syndromes. We review recent findings related to the biochemical mechanisms that predispose to malignant transformation in each condition. Key genetic discoveries such as novel mutations, degrees of penetrance, principles of the two-hit hypothesis, and co-occurrence of multiple mutations are shared. Clinical pearls, such as information regarding epidemiology, natural history, or prognosis, are also discussed. Germline mutations predisposing to pediatric myeloid neoplasms are frequent, but underrecognized. They hold major clinical implications regarding prognosis, treatment strategies, and screening for other malignancies. Further research is warranted to better characterize each of these conditions, as well as identify additional novel germline pathogenic variants of interest.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10620955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Value in Myeloma Care: Myth or Reality.","authors":"Evguenia Ouchveridze,&nbsp;Katherine Berger,&nbsp;Ghulam Rehman Mohyuddin","doi":"10.1007/s11899-022-00669-1","DOIUrl":"https://doi.org/10.1007/s11899-022-00669-1","url":null,"abstract":"<p><strong>Purpose of review: </strong>Despite tremendous advances in multiple myeloma (MM) care, the disease maintains considerable morbidity and requires long-term treatment associated with significant financial toxicity to patients and high costs to society. In this review, we explore why - despite treatment advances - value in MM treatment is largely a myth, then explain some ways the myth might become a reality.</p><p><strong>Recent findings: </strong>We discuss how value-based care in MM should include patient-centered outcomes such as financial toxicity and quality of life, which are heavily impacted by cost of drugs and the indefinite duration of therapy that is standard in MM treatment. We propose multiple paths to work toward reducing cost and augmenting value of care for patients with MM, including improving access to generic drugs, increasing federal funding for clinical trials, designing more patient-centric clinical trials, and exploring the utilization of minimal residual disease (MRD)-driven treatment de-escalation, among others. We remain optimistic that despite the challenges, we can work toward making progress in the realm of value-based care for patients with MM and make it a reality.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10620941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bispecific Antibodies for the Treatment of Multiple Myeloma.","authors":"Scott R Goldsmith,&nbsp;Shawn Streeter,&nbsp;Fahrettin Covut","doi":"10.1007/s11899-022-00675-3","DOIUrl":"https://doi.org/10.1007/s11899-022-00675-3","url":null,"abstract":"<p><strong>Purpose of review: </strong>Advances in multiple myeloma therapies have greatly improved outcomes for patients living with the disease, although to date there is yet to be a cure. Cellular and immunotherapies, approved or in development, offer the promise of significantly advancing toward that possibility. The aim of this review is to provide a synopsis and commentary on the current and future states of bispecific agents aimed at harnessing the antineoplastic potential of T-cells in treating and eradicating myeloma.</p><p><strong>Recent findings: </strong>Numerous bispecific agents are in clinical development with some on the precipice of regulatory approval. While BCMA remains the principal target, some agents are directed at novel targets such as GPRC5D and FcRH5. The constructs vary in design and pharmacokinetics which has dosing and administration implications. The toxicity profiles of these agents generally reflect that of other immune therapies, including cytokine release syndrome and rarely neurotoxicity, although immunosuppression has also led to elevated infection risks. However, the toxicities are generally manageable and offset by unprecedented efficacy seen in such heavily pretreated cohorts. Bispecific agents are poised to significantly alter the treatment paradigms for myeloma. They provide a convenient \"off-the-shelf\" platform with often deep and durable responses. Toxicities are often limited in duration and severity. In the early-phase trials, many patients have been able to remain on treatment for extended periods, even among those with high-risk features. Upcoming trials are likely to explore earlier implementation of these agents in order to offer this therapeutic opportunity to broader cohorts.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10668759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}