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Forthcoming Issues
Malignancies of the Upper Gastrointestinal Tract (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - February 27, 2024 Category: Cancer & Oncology Source Type: research

Advances in Gastric Cancer Surgical Management
The goal of a gastric cancer operation is a microscopically negative resection margin and D2 lymphadenectomy. Minimally invasive techniques (laparoscopic and robotic) have been proven to be equivalent for oncologic care, yet with faster recovery. Endoscopic mucosal resection can be used for T1a N0 tumor resection. Better understanding of hereditary gastric cancer and molecular subtypes has led to specialized recommendations for MSI-high tumors and patients with pathogenic CDH1 mutations. In the future, surgical management will support minimally invasive approaches and personalized cancer care based on subtype. (Source: Hem...
Source: Hematology/Oncology Clinics of North America - February 23, 2024 Category: Cancer & Oncology Authors: Emily E. Stroobant, Vivian E. Strong Source Type: research

Malignancies of the Upper Gastrointestinal Tract
Treatment of upper gastrointestinal (GI) cancers has undergone a significant transformation over the past decade. The move to minimally invasive surgical approaches has led to potential better surgical therapy tolerance, lessening of surgical complications and enhanced recovery times, and potential enhancement of delivery of adjuvant therapies. Adjuvant treatment has advanced across the spectrum of GI cancers with improved survival with more contemporary chemotherapy regimens. Increasingly neoadjuvant strategies are being employed across the spectrum of upper GI malignancies, and participation in multidisciplinary discussi...
Source: Hematology/Oncology Clinics of North America - February 19, 2024 Category: Cancer & Oncology Authors: David H. Ilson Tags: Preface Source Type: research

Cereblon-Targeting Ligase Degraders in Myeloma
Cereblon-targeting degraders, including immunomodulatory imide drugs lenalidomide and pomalidomide alongside cereblon E3 ligase modulators like iberdomide and mezigdomide, have demonstrated significant anti-myeloma effects. These drugs play a crucial role in diverse therapeutic approaches for multiple myeloma (MM), emphasizing their therapeutic importance across various disease stages. Despite their evident efficacy, approximately 5% to 10% of MM patients exhibit primary resistance to lenalidomide, and resistance commonly develops over time. Understanding the intricate mechanisms of action and resistance to this drug class...
Source: Hematology/Oncology Clinics of North America - January 31, 2024 Category: Cancer & Oncology Authors: Holly Lee, Paola Neri, Nizar J. Bahlis Source Type: research

Proteasome Inhibitors in Multiple Myeloma
During the last 20 years, proteasome inhibitors have been a cornerstone for the therapeutic management of multiple myeloma (MM). This review highlights how MM research has evolved over time in terms of our understanding of the mechanistic basis for the pronounced clinical activity of proteasome inhibitors in MM, compared with the limited clinical applications of this drug class outside the setting of plasma cell dyscrasias (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - January 25, 2024 Category: Cancer & Oncology Authors: Constantine S. Mitsiades Source Type: research

Dedication
Remembering the Contributions of W. Michael Kuehl, MD (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - January 24, 2024 Category: Cancer & Oncology Authors: Peter Leif Bergsagel Source Type: research

Role of Consolidation and Maintenance
Consolidation therapy consists of short-term therapy after stem cell transplant in multiple myeloma. Key consolidation trials have shown mixed results on whether consolidation should be included after transplant, leading to varied clinical practice. Maintenance therapy consists of long-term, typically fixed-duration or indefinite, therapy. Standard-risk patients typically receive single-agent therapy, whereas high-risk may benefit from doublet therapy and beyond. Adverse events and quality of life concerns should be considered, as optimal duration of maintenance therapy continues to be studied. (Source: Hematology/Oncology...
Source: Hematology/Oncology Clinics of North America - January 22, 2024 Category: Cancer & Oncology Authors: Anupama D. Kumar, Ajai Chari Source Type: research

Immunocompetent Mouse Models of Multiple Myeloma
Immunocompetent mouse models of multiple myeloma (MM) are particularly needed in the era of T  cell redirected therapy to understand drivers of sensitivity and resistance, optimize responses, and prevent toxicities. Three mouse models have been extensively characterized: the Balb/c plasmacytomas, the 5TMM, and the Vk*MYC. In the last year, additional models have been generated, which, for t he first time, capture primary MM initiating events, like MMSET/NSD2 or cyclin D1 dysregulation. However, the long latency needed for tumor development and the lack of transplantable lines limit their utilization. Future studies should...
Source: Hematology/Oncology Clinics of North America - January 16, 2024 Category: Cancer & Oncology Authors: Megan Du, Peter Leif Bergsagel, Marta Chesi Source Type: research

New Therapies on the Horizon for Relapsed Refractory Multiple Myeloma
Despite improved treatments, most patients with multiple myeloma (MM) will experience relapse. Several novel agents have demonstrated activity and tolerability in early phase clinical trials. Venetoclax is a B-cell lymphoma 2 (Bcl-2) inhibitor with activity in patients with t(11;14) and/or Bcl-2 expression. Iberdomide and mezigdomide are cereblon E3 ligase modulators with higher potency, immunomodulatory, and antiproliferative activity compared with lenalidomide and pomalidomide. They have shown promising activity in heavily pretreated patients. Modakafusp alfa is an immunocytokine that targets interferons to CD38+ cells. ...
Source: Hematology/Oncology Clinics of North America - January 11, 2024 Category: Cancer & Oncology Authors: Nadine Abdallah, Shaji K. Kumar Source Type: research

Bispecific Antibodies in the Treatment of Multiple Myeloma
The treatment of multiple myeloma (MM) is evolving rapidly. In recent years, T-cell-based novel immunotherapies emerged as new treatment strategies for patients with relapsed/refractory MM, including highly effective new options like chimeric antigen receptor (CAR)-modified T  cells and bispecific antibodies (bsAbs). Currently, B-cell maturation antigen is the most commonly used target antigen for CAR T-cell and bsAb therapies in MM. Results from different clinical trials have demonstrated promising efficacy and acceptable safety profile of bsAb in RRMM. (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - January 9, 2024 Category: Cancer & Oncology Authors: Xiang Zhou, Xianghui Xiao, Klaus Martin Kortuem, Hermann Einsele Source Type: research

Molecular Pathogenesis of Multiple Myeloma
Multiple myeloma is a malignancy of bone-marrow-localized, isotype-switched plasma cells that secrete a monoclonal immunoglobulin and cause hyperCalcemia, Anemia, Renal failure, and lytic Bone disease. It is preceded, often for decades, by a relatively stable monoclonal gammopathy lacking these clinical and malignant features. Both conditions are characterized by the presence of types of immunoglobulin heavy gene translocations that dysregulate a cyclin D family gene on 11q13 (CCND1), 6p21 (CCND3), or 12q11 (CCND2), a maf family gene on 16q23 (MAF), 20q11 (MAFB), or 8q24 (MAFA), or NSD2/FGFR3 on 4p16, or the presence of hy...
Source: Hematology/Oncology Clinics of North America - January 9, 2024 Category: Cancer & Oncology Authors: Francesco Maura, Peter Leif Bergsagel Source Type: research

Approach to High-Risk Multiple Myeloma
Improving the outcome of high-risk myeloma (HRMM) is a key therapeutic aim for the next decade. To achieve this aim, it is necessary to understand in detail the genetic drivers underlying this clinical behavior and to target its biology therapeutically. Advances have already been made, with a focus on consensus guidance and the application of novel immunotherapeutic approaches. Cases of HRMM are likely to have impaired prognosis even with novel strategies. However, if disease eradication and minimal disease states are achieved, then cure may be possible. (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - January 8, 2024 Category: Cancer & Oncology Authors: Xiaoyi Chen, Gaurav Varma, Faith Davies, Gareth Morgan Source Type: research

Immune-Pathogenesis of Myeloma
This research indicates that monoclonal gammopathy of undetermined significance (MGUS) and myeloma may stem from chronic immune activation and inflammation, causing immune dysfunction and spatial immune exclusion. As the conditions progress, a shift toward myeloma involves ongoing immune impairment, affecting both innate and adaptive immunity. Intriguingly, even in advanced myeloma stages, susceptibility to immune effector cells persists. This insight highlights the intricate interplay between immune responses and the development of these conditions, paving the way for potential therapeutic interventions targeting immune m...
Source: Hematology/Oncology Clinics of North America - January 8, 2024 Category: Cancer & Oncology Authors: Madhav V. Dhodapkar Source Type: research

Impact of Clonal Heterogeneity in Multiple Myeloma
Multiple myeloma is characterized by a highly heterogeneous disease distribution within the bone marrow-containing skeletal system. In this review, we introduce the molecular mechanisms underlying clonal heterogeneity and the spatio-temporal evolution of myeloma. We discuss the clinical impact of clonal heterogeneity, which is thought to be one of the biggest obstacles to overcome therapy resistance and to achieve cure. (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - January 8, 2024 Category: Cancer & Oncology Authors: Carolina Schinke, Leo Rasche, Marc S. Raab, Niels Weinhold Source Type: research

Measurable Residual Disease and Decision-Making in Multiple Myeloma
Measurable (minimal) residual disease (MRD) has already proven to be one of the most important prognostic factors in multiple myeloma (MM). Each improvement in the depth of MRD testing has led to superior discrimination of outcomes, and sustained MRD negativity seems to be paramount to durable responses. Peripheral blood assays to assess for MRD are still under investigation but hold promise as complementary tools to bone marrow MRD assays such as next-generation sequencing and flow cytometry. Herein, the authors explore the evidence and potential benefits and drawbacks of MRD-adapted clinical decision-making in MM. (Sourc...
Source: Hematology/Oncology Clinics of North America - January 6, 2024 Category: Cancer & Oncology Authors: Benjamin A. Derman, Rafael Fonseca Source Type: research