Introduction Chronic Lymphocytic Leukemia. Where Do We Stand, Where Do We Go
No abstract available (Source: The Cancer Journal)
Source: The Cancer Journal - July 1, 2021 Category: Cancer & Oncology Tags: Introduction From the Guest Editor Source Type: research

Minimal Residual Disease in Multiple Myeloma: Ready for Prime Time?
Minimal residual disease (MRD) techniques are essential to identify the small clonal fraction within and outside the bone marrow. In the last years, evidence regarding their prognostic role for the evaluation of the depth of response of current treatment strategies has grown rapidly. Consequently, MRD was incorporated in an increasing number of clinical trials for multiple myeloma patients, also as primary endpoint, and even to guide therapeutic choices. A robust correlation between MRD negativity and survival was established. Yet, several issues regarding MRD evaluation remain to be addressed: from the optimal and more co...
Source: The Cancer Journal - May 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research

An Overview of Organoid and 3-Dimensional Models in Multiple Myeloma
Multiple myeloma is a hematological malignancy of differentiated B cells that resides primarily in bone marrow niches. Its interaction with the microenvironment is known to provide a survival advantage and plays an important role in drug resistance. Despite the increased efficacy of new treatment drugs, clinical results oftentimes fall short of in vitro observations, and this disease remains incurable. Conventional 2-dimensional cultures used to perform chemosensitivity assays and the established multiple myeloma cells lines commonly used do not replicate the conditions seen in vivo. This review presents various 3-dimensio...
Source: The Cancer Journal - May 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Maintenance Strategies for Myeloma: Is Bigger Always Better?
Over the last decade, several very important prospective randomized controlled trials have confirmed the significant survival benefit conferred by maintenance therapies. Owing to these developments, the role of continued maintenance in the optimal management strategies of newly diagnosed myeloma patients (both transplant-eligible and transplant-ineligible) has been strongly cemented. In dealing with an incurable disease such as myeloma, whether to offer maintenance is no longer as relevant a question as it was before, but which antimyeloma agent or agents to use, as maintenance remains more pertinent today. More importantl...
Source: The Cancer Journal - May 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Monoclonal Antibodies in Myeloma: Optimizing Targeted Therapy
In the past several years, there have been significant advances in the therapeutic arsenal of agents used to treat multiple myeloma (MM). Despite these advances, MM remains incurable. One of the most recent therapeutic advances is the development of targeted monoclonal antibodies (MoAbs). The MoAbs have significantly improved disease response rates, and extended survival in MM patients. In this review, we highlight the current US Food and Drug Administration approved MoAbs, namely, belantamab mafodotin, daratumumab, elotuzumab, and isatuximab. The mechanisms of action and pivotal clinical trials that led to US Food and Dru...
Source: The Cancer Journal - May 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research

From Bench to Bedside: The Evolution of Genomics and Its Implications for the Current and Future Management of Multiple Myeloma
The summation of 20 years of biological studies and the comprehensive analysis of more than 1000 multiple myeloma genomes with data linked to clinical outcome has enabled an increased understanding of the pathogenesis of multiple myeloma in the context of normal plasma cell biology. This novel data have facilitated the identification of prognostic markers and targets suitable for therapeutic manipulation. The challenge moving forward is to translate this genetic and biological information into the clinic to improve patient care. This review discusses the key data required to achieve this and provides a framework within whi...
Source: The Cancer Journal - May 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Chimeric Antigen Receptor T-Cell Therapeutics for Multiple Myeloma: Moving Into the Spotlight
Chimeric antigen receptor (CAR) T-cell therapy has quickly emerged as a highly promising treatment for patients with relapsed and refractory multiple myeloma. There are numerous candidates under development, each with their unique characteristics and points of differentiation. The most recent US Food and Drug Administration approval of the first B-cell maturation antigen–targeted CAR-T cell therapy on March 26, 2021, has paved a path forward for the eventual evaluation of more of these investigational agents undergoing clinical trials. Herein, we highlight, from a clinical development perspective, the CAR-T cell therapie...
Source: The Cancer Journal - May 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Strategies to Overcome High-Risk Multiple Myeloma
Multiple myeloma (MM) patients with high-risk cytogenetics continue to have inferior outcomes despite recent advances in the treatment of MM. As defined by the International Myeloma Working Group, the presence of t(4;14), t(14;16), del(17p), t(14;20) and amplification of 1q are considered to be high-risk chromosomal abnormalities associated with poor survival. Despite the use of immunomodulatory agents, proteasome inhibitors, autologous stem cell transplantation, and anti-CD38 monoclonal antibodies, clinical trials of current therapies have not shown strong statistical evidence of being able to overcome the poor prognosis ...
Source: The Cancer Journal - May 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Induction Therapy Strategies in the Transplant-Ineligible Population
Multiple myeloma (MM), a plasma cell malignancy, accounts for ~10% of hematologic malignancies and predominantly affects the older population. It exhibits a heterogeneous biology and a complex genetic phenotype that affect patient prognosis. The treatment of MM has evolved significantly over the last decade with the use of autologous stem cell transplantation and several novel agents. Consequently, outcomes have improved in this time period, with the most impact in younger patients. Management of MM in elderly frail patients requires a thoughtful approach as majority of these patients carry multiple comorbidities and are p...
Source: The Cancer Journal - May 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research

From VAD to VRD: Is Transplant Still Needed in the Upfront Setting of Myeloma?
High-dose therapy followed by autologous stem cell transplantation (ASCT) is considered the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (MM). With new treatment combinations offering the advantage of improved clinical outcomes of MM patients, the utilization of ASCT is again being addressed in the evolving treatment landscape. In this article, we review the role of frontline ASCT in the management of patients with MM. (Source: The Cancer Journal)
Source: The Cancer Journal - May 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Smoldering Myeloma Treatment: Who, What, and When
Smoldering multiple myeloma (MM) is a clonal plasma cell disorder characterized by excess marrow involvement and immunoglobulin production. It is the precursor of MM, differing by the lack of end-organ damage. Smoldering MM encompasses a heterogeneous group of patients, with a median risk of progression to active disease of 50% in the first 5 years. Until recently, the standard of care would dictate observation off therapy until the development of end-organ damage. The recognition of high-risk and ultrahigh-risk subgroups of smoldering MM, with more likely evolution to MM, has led to earlier initiation of therapy in the di...
Source: The Cancer Journal - May 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Multiple Myeloma: “If You Don't Stop to Look Around Once in a While… You Could Miss It”
No abstract available (Source: The Cancer Journal)
Source: The Cancer Journal - May 1, 2021 Category: Cancer & Oncology Tags: Introduction From the Guest Editor Source Type: research

Off-the-Shelf Chimeric Antigen Receptor T Cells: How Do We Get There?
Banked chimeric antigen receptor (CAR) T cells immediately available for off-the-shelf (OTS) application can solve key limitations of patient-specific CAR T-cell products while retaining their potency. The allogeneic nature of OTS cell therapies requires additional measures to minimize graft-versus-host disease and host-versus-graft immune rejection in immunocompetent recipients. In this review, we discuss engineering and manufacturing strategies aimed at minimizing unwanted interactions between allogeneic CAR T cells and the host. Overcoming these limitations will improve safety and antitumor potency of OTS CAR T cells an...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Is Adoptive Cellular Therapy With Non–T-Cell Immune Effectors the Future?
Success from checkpoint blockade and adoptive cell therapy has brought a new hope in cancer immunotherapy. Adoptive cell therapy involves the isolation of immune cells, ex vivo activation and/or expansion, and reinfusion into the patients, and their effect can be dramatically increased by the incorporation of chimeric antigen receptors specific to molecules expressed on tumor cells. Chimeric antigen receptor T cells have shown exciting results in the treatment of liquid malignancies; nevertheless, they suffer from limitations including severe adverse effects such as cytokine release syndrome and neurotoxicity seen in patie...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Using Adoptive Cellular Therapy for Localized Protein Secretion
Redirection of T cell cytotoxicity by the chimeric antigen receptor (CAR) structure may not be sufficient for optimal antitumor function in the patient tumor microenvironment. Comodifying CAR T cells to secrete different classes of proteins can be used to optimize CAR T cell function, overcome suppressive signals, and/or alter the tumor microenvironment milieu. These modifications aim to improve initial responses to therapy and enhance the durability of response. Furthermore, CAR T cells can deliver these molecules locally to the tumor microenvironment, avoiding systemic distribution. This approach has been tested in precl...
Source: The Cancer Journal - March 1, 2021 Category: Cancer & Oncology Tags: Review Articles Source Type: research