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Current Hematologic Malignancy Reports

Shalin Kothari, Jens Hillengass, Philip L McCarthy, Sarah A Holstein
PURPOSE OF REVIEW: The 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 FINDINGS: A 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)...
January 22, 2019: Current Hematologic Malignancy Reports
Stacie Ittershagen, Solveig Ericson, Lamis Eldjerou, Ali Shojaee, Eric Bleickardt, Manisha Patel, Tetiana Taran, Oezlem Anak, Charlene Hall, Mimi Leung, Deborah Roccoberton, Florence Salmon, Miriam Fuchs, Vadim Romanov, David Lebwohl
PURPOSE OF REVIEW: 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 FINDINGS: Tisagenlecleucel 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 adult patients with relapsed or refractory (r/r) acute lymphoblastic leukemia, followed by approval in May 2018 for a second indication in adult patients with r/r diffuse large B cell lymphoma...
January 21, 2019: Current Hematologic Malignancy Reports
Myo Htut
PURPOSE OF REVIEW: The 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...
January 21, 2019: Current Hematologic Malignancy Reports
Sarah A Holstein, Vera J Suman, Philip L McCarthy
PURPOSE OF REVIEW: While 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 FINDINGS: A 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 survival (PFS)...
January 19, 2019: Current Hematologic Malignancy Reports
Guru Subramanian Guru Murthy, Ehab Atallah
PURPOSE OF REVIEW: Chronic 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 FINDINGS: Several 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...
January 15, 2019: Current Hematologic Malignancy Reports
Bronwen E Shaw
PURPOSE OF REVIEW: Graft versus host disease (GVHD) is a common complication following hematopoietic cell transplant and is associated with a high symptom burden, reduced functional status, and impaired quality of life (QOL). QOL is best assessed by patient-reported outcomes (PRO). Numerous clinical trials for the prevention and treatment of GVHD are available. This review aims to understand the landscape of PRO inclusion in clinical trials for GVHD over the last decade. RECENT FINDINGS: Consensus bodies, including experts in GVHD, PRO, and clinical trials have made recommendations for a standardized approach for the inclusion of PRO in clinical trials including as primary outcomes, however, these have yet to be implemented in a consistent manner in practice...
January 14, 2019: Current Hematologic Malignancy Reports
Maliha Khan, Tanya Siddiqi
PURPOSE OF REVIEW: While chemoimmunotherapy has improved outcomes in chronic lymphocytic leukemia (CLL), it is not curative, has significant relapse rates, and is not always well tolerated. Recently, novel targeted therapies have been developed to increase response rates and reduce toxicity, especially in high-risk disease. Current goals of CLL therapies are to produce deep and durable, especially minimal residual disease (MRD)-negative, remissions so as to allow patients to ultimately discontinue treatment for a while...
December 2018: Current Hematologic Malignancy Reports
Franklin Fuda, Weina Chen
PURPOSE OF REVIEW: Minimal or measurable residual disease (MRD) detected by multiparameter flow cytometry (MFC) is an independent prognostic indicator in acute leukemia. However, the predictive value of MFC MRD is affected by technical challenges, interpretive complexities, and inadequate standardization, particularly in acute myeloid leukemia (AML). Here, we critically review the methodological principles of the MFC MRD assay and discuss clinical implications of MRD. RECENT FINDINGS: Key components of MFC MRD assays to be discussed include the principles of MFC, panel selection, analysis approaches, level of quantifiable MRD and calculation, reporting, and areas of improvements...
December 2018: Current Hematologic Malignancy Reports
Helen Ma, Ahmed Sawas
PURPOSE OF REVIEW: This review is about the antibody-drug conjugate (ADC), a form of drug delivery consisting of a monoclonal antibody, linker, and cytotoxic payload. We summarize the history of ADC development, highlighting the three FDA-approved ADCs currently available. RECENT FINDINGS: Gemtuzumab ozogamicin is a CD33-targeted ADC linked to calicheamicin. It is approved for CD33+ AML in the first line or the relapsed or refractory (R/R) setting. Brentuximab vedotin is a CD30-targeted ADC bound to MMAE...
December 2018: Current Hematologic Malignancy Reports
Maria Sanz-De Pedro, Wei Wang, Rashmi Kanagal-Shamanna, Joseph D Khoury
PURPOSE OF REVIEW: This review provides a comprehensive update of myelodysplastic syndromes (MDS) and their diagnostic criteria, with emphasis on novel concepts and state-of-the-art laboratory workup, including multiparameter/multicolor flow cytometry, chromosome analysis, and mutation profiling. RECENT FINDINGS: Recent advances in genetics and molecular technologies have provided unprecedented insights into the pathogenic mechanisms and genomic landscape of MDS and its precursor lesions...
December 2018: Current Hematologic Malignancy Reports
Sanam Loghavi, Joseph D Khoury
PURPOSE OF REVIEW: The goal of this review is to provide a practical and comprehensive update on changes in the classification of chronic myelomonocytic leukemia (CMML) and a summary of the most recent developments in our understanding of its genomic landscape, prognostic models, and therapeutic approaches. RECENT FINDINGS: The 2017 revision of the World Health Organization (WHO) classification includes substantial changes to the subclassification CMML. The clinical utility of the newly revised subclassification scheme is discussed...
December 2018: Current Hematologic Malignancy Reports
Roberta Zappasodi, Jedd D Wolchok, Taha Merghoub
The original version of this article unfortunately contained a mistake. The conflict of interest statement was incorrect. The corrected statement is given below.
November 8, 2018: Current Hematologic Malignancy Reports
Ting Zhou, L Jeffrey Medeiros, Shimin Hu
PURPOSE OF REVIEW: In this review, we emphasize up-to-date practical cytogenetic and molecular aspects of chronic myeloid leukemia (CML) and summarize current knowledge on tyrosine kinase inhibitor (TKI) resistance and treatment response monitoring of CML. RECENT FINDINGS: The introduction of TKIs has changed the natural course of CML and markedly improved patient survival. Over the past decades, many research efforts were devoted to elucidating the leukemogenic mechanisms of BCR-ABL1 and developing novel TKIs...
October 29, 2018: Current Hematologic Malignancy Reports
Robert Havard, Deborah M Stephens
PURPOSE OF REVIEW: This article will review the use of anti-CD19 CAR-T therapy used in relapsed/refractory diffuse large B cell lymphoma. RECENT FINDINGS: The clinical outcomes, safety analysis, and other relevant considerations will be discussed with an emphasis on the most recently published data regarding the ZUMA-1, JULIET, and TRANSCEND NHL-001 trials. Anti-CD19 CAR-T therapy is an exciting new therapy now approved and available to patients with relapsed/refractory diffuse large B cell lymphoma...
October 25, 2018: Current Hematologic Malignancy Reports
Bing Li, John O Mascarenhas, Raajit K Rampal
PURPOSE OF REVIEW: Although BCR-ABL1-negative myeloproliferative neoplasms (MPN) are chronic, clonal hematopoietic stem cell (HSC) disorders marked by proliferation of one or more myeloid lineages, a substantial proportion of patients transform to acute myeloid leukemia. Leukemic transformation (LT) from a pre-existing MPN carries a dismal prognosis. Here, we review recent genetic, biological, and clinical data regarding LT. RECENT FINDINGS: In the last decade, DNA sequencing has revolutionized our understanding of the genomic landscape of LT...
October 23, 2018: Current Hematologic Malignancy Reports
Joseph D Khoury
PURPOSE OF REVIEW: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare malignancy derived from plasmacyoid dendritic cells whose biology, clinical features, and treatment options are increasingly better understood. RECENT FINDINGS: TCF4 is a master regulator that drives donwstream transcriptional programs in BPDCN. In turn, TCF4 activity is dependent on the bromodomain and extra-terminal domain (BET) protein BRD4 whose inhibition provides a promising therapeutic vulnerability...
October 22, 2018: Current Hematologic Malignancy Reports
P Rastogi, A K Deva, H Miles Prince
PURPOSE OF REVIEW: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognised malignancy of T lymphocytes exclusively associated with textured breast implants. This review aims to evaluate existing theories regarding the epidemiology, pathogenesis, clinical evaluation and management of the disease. RECENT FINDINGS: The true incidence of BIA-ALCL is difficult to define. Prevailing pathogenic theories recognise the interplay between textured implants, Gram-negative bacteria, host genetics (e...
October 22, 2018: Current Hematologic Malignancy Reports
Naveen Pemmaraju, Audun Utengen, Vikas Gupta, Michael A Thompson, Andrew A Lane
PURPOSE OF REVIEW: Engagement on social media for professional, healthcare-related communication is rapidly rising around the world. We aimed to better understand the dynamics of a rare disease Twitter hashtag community. RECENT FINDINGS: Twitter has served as a platform for academic discussion, a method for knowledge dissemination directly from medical meetings, and a venue for patient caregiver and support groups. One example of a rare cancer that has seen an increase in available information via Twitter is blastic plasmacytoid dendritic cell neoplasm, or BPDCN...
October 18, 2018: Current Hematologic Malignancy Reports
Bei Hu, Ryan Jacobs, Nilanjan Ghosh
PURPOSE OF THE REVIEW: The ligation of PD-1 with PD-L1 activates a critical immune checkpoint leading to T cell dysfunction, exhaustion, and tolerance. Anti-PD-1 or anti-PD-L1 monoclonal antibodies can reverse the immune checkpoint, releasing the brake on T cell responses. We provide a comprehensive review of the literature on the activity of checkpoint inhibitors in lymphoma. RECENT FINDINGS: We discuss the latest findings with checkpoint inhibitors in lymphoma and new promising studies incorporating these agents...
October 18, 2018: Current Hematologic Malignancy Reports
Sagar S Patel, Navneet S Majhail
PURPOSE OF REVIEW: Social media has dramatically changed the access and exchange of information in healthcare and beyond. A variety of platforms and resources exist allowing blood and marrow transplant providers, researchers, and patients to interact. We review the adoption of social media by the transplantation community. RECENT FINDINGS: Social media allows on-demand access to the latest developments at national and international meetings, newly published research articles, facilitates networking with colleagues, participation in advocacy, and promoting available clinical trials...
October 15, 2018: Current Hematologic Malignancy Reports
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