Multiple Myeloma: A Review of the Literature and a Case Report Highlighting the Immunocompromised State of Myeloma Patients

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Abstract

Multiple myeloma (MM), a malignancy involving plasma cells, disproportionately affects older adults with an average age of diagnosis of about 70 years. Oftentimes, the therapies used in the treatment of MM are associated with a risk for immunotoxicity, lowering the ability of the immune system to fight off opportunistic infections. This is an important relationship for clinicians to realize as the incidence of opportunistic infections in myeloma patients is increasing. As an example, we present a case of a patient with MM who subsequently developed a cryptococcal infection. Our paper will highlight the key details of the case as well as shed light on the importance of understanding the immunodeficiencies in this patient population. We highlight important aspects of the current literature related to MM and relate them to the associated case.

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Cancer statistics, 2020

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2020)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.

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Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013.

Joseph Mikhael, David Dingli, Vivek Roy … (2013)

Multiple myeloma remains an incurable neoplasm of plasma cells that affects more than 20,000 people annually in the United States. There has been a veritable revolution in this disease during the past decade, with dramatic improvements in our understanding of its pathogenesis, the development of several novel agents, and a concomitant doubling in overall survival. Because multiple myeloma is a complex and wide-ranging disorder, its management must be guided by disease- and patient-related factors; emerging as one of the most influential factors is risk stratification, primarily based on cytogenetic features. A risk-adapted approach provides optimal therapy to patients, ensuring intense therapy for aggressive disease and minimizing toxic effects, providing sufficient but less intense therapy for low-risk disease. This consensus statement reflects recommendations from more than 20 Mayo Clinic myeloma physicians, providing a practical approach for newly diagnosed patients with myeloma who are not enrolled in a clinical trial. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

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Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells

Mohamed-Reda Benmebarek, Clara Helke Karches, Bruno Cadilha … (2019)

Effective adoptive T cell therapy (ACT) comprises the killing of cancer cells through the therapeutic use of transferred T cells. One of the main ACT approaches is chimeric antigen receptor (CAR) T cell therapy. CAR T cells mediate MHC-unrestricted tumor cell killing by enabling T cells to bind target cell surface antigens through a single-chain variable fragment (scFv) recognition domain. Upon engagement, CAR T cells form a non-classical immune synapse (IS), required for their effector function. These cells then mediate their anti-tumoral effects through the perforin and granzyme axis, the Fas and Fas ligand axis, as well as the release of cytokines to sensitize the tumor stroma. Their persistence in the host and functional outputs are tightly dependent on the receptor’s individual components—scFv, spacer domain, and costimulatory domains—and how said component functions converge to augment CAR T cell performance. In this review, we bring forth the successes and limitations of CAR T cell therapy. We delve further into the current understanding of how CAR T cells are designed to function, survive, and ultimately mediate their anti-tumoral effects.

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Author and article information

Journal

Journal ID (nlm-ta): World J Oncol

Journal ID (iso-abbrev): World J Oncol

Journal ID (publisher-id): Elmer Press

Title: World Journal of Oncology

Publisher: Elmer Press

ISSN (Print): 1920-4531

ISSN (Electronic): 1920-454X

Publication date (Print): June 2024

Publication date (Electronic): 15 April 2024

Volume: 15

Issue: 3

Pages: 348-354

Affiliations

[a ]Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ, USA

[b ]Hackensack Meridian School of Medicine, Nutley, NJ, USA

[c ]Department of Hematology and Oncology, Jersey Shore University Medical Center, Neptune, NJ, USA

[d ]Department of Pulmonology, Jersey Shore University Medical Center, Neptune, NJ, USA

[e ]Department of Infectious Disease, Jersey Shore University Medical Center, Neptune, NJ, USA

Author notes

[f ]Corresponding Author: Brandon Nightingale, Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ 07753, USA. Email: brandon.nightingale@ 123456hmhn.org

Article

DOI: 10.14740/wjon1780

PMC ID: 11092413

PubMed ID: 38751697

SO-VID: 93977f22-6527-4544-9e9b-c91ffce10208

License:

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 29 November 2023

Date accepted : 5 February 2024

Funding

None to declare.

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Multiple Myeloma: A Review of the Literature and a Case Report Highlighting the Immunocompromised State of Myeloma Patients

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Cancer Immunotherapy

Most cited references 37

Cancer statistics, 2020

Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013.

Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells

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