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New Biological Therapies for Multiple Myeloma.

Multiple myeloma is a cancer of bone marrow plasma cells that represents approximately 10% of hematologic malignancies. Though it is typically incurable, a remarkable suite of new therapies developed over the last 25 years has enabled durable disease control in most patients. This article briefly introduces the clinical features of multiple myeloma and aspects of multiple myeloma biology that modern therapies exploit. Key current and emerging treatment modalities are then reviewed, including cereblon-modulating agents, proteasome inhibitors, monoclonal antibodies, other molecularly targeted th…

[CAR-T therapy for multiple myeloma].

Immune cell therapies targeting B-cell maturation antigen (BCMA) have been developed for relapsed and refractory multiple myeloma (RR-MM). Chimeric antigen receptor (CAR)-T cell therapies appear promising for RR-MM, and two BCMA-targeting CAR-T cell products, idecabtagene vicleucel and ciltacabtagene autoleucel, have achieved the highest response rates in heavily treated patients to date. These CAR-T products have been approved for RR-MM previously treated with 3 agents (proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies) in Japan. Despite the promising efficacy of CAR-T t…

Current Main Topics in Multiple Myeloma.

Multiple Myeloma (MM) remains a difficult to treat disease mainly due to its biological heterogeneity, of which we are more and more knowledgeable thanks to the development of increasingly sensitive molecular methods that allow us to build better prognostication models. The biological diversity translates into a wide range of clinical outcomes from long-lasting remission in some patients to very early relapse in others. In NDMM transplant eligible (TE) patients, the incorporation of mAb as daratumumab in the induction regimens, followed by autologous stem cell transplantation (ASCT) and consol…

Understanding high-risk smoldering multiple myeloma.

Smoldering multiple myeloma (SMM) is an asymptomatic condition with heterogeneous biology and various risks of progression to symptomatic disease. The best-known risk stratification models are Mayo-2018, and IWWG based on tumor burden. Recently, the personalized risk assessment tool PANGEA was introduced. New markers of SMM progression, including genomic and immune characteristics of plasma cells (PCs) and tumor microenvironment, are under investigation, and some have been incorporated into traditional scoring systems. Only one phase 3 clinical trial demonstrated an overall survival benefit of…

Antibody Drug Conjugates in Multiple Myeloma.

Antibody-drug conjugates (ADCs) have emerged as a treatment option for patients with relapsed/refractory multiple myeloma with the regulatory approval of the first-in-class B-cell maturation antigen (BCMA) ADC belantamab mafodotin. Other BCMA and non-BCMA ADCs are currently in clinical development. Whereas ADCs allow antigen-specific delivery of a chemomoiety to myeloma cells, on-target and off-target effects related to antigen target, antibody, linker, and chemomoiety can also limit these approaches. We review the clinical development of belantamab mafodotin and ongoing efforts to enhance its…

Steps towards a Multiple Myeloma Cure?

Multiple myeloma survival has increased in last 20 years because of new treatments, better clinical management due to novel diagnostic tools such as imaging, and better understanding of the disease, biologically and genetically. Novel drugs have been introduced that act with different therapeutic mechanisms, but so have novel therapeutic strategies such as consolidation and maintenance after autologous stem cell transplant. Imaging (such as PET-CT and MRI) has been applied at diagnosis and after therapy for minimal residual disease monitoring. Multiparametric flow and molecular NGS may detect,…

ASH Highlights and Commentary: Multiple Myeloma

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Совпадение в полном тексте источника
… Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia, 33(9), 2266–2275. https://doi.org/10.1038/s41375-019-0435-7 Mohan, M., Hari, P., & Dhakal, B. (2021). Immunotherapy in multiple myeloma—time for a second major paradigm shift. … Antibody treatment in multiple myeloma. (2021). Clinical Advances in Hematology & Oncology, 19(3), 166–174. https://www.hematologyandoncology.net/archives/march-2021/antibody-treatment-in-multiple-myeloma/ …

How I approach smoldering multiple myeloma.

The current standard of care in smoldering multiple myeloma (SMM) is close surveillance, outside of clinical trials. Efforts are being made to understand the pathobiologic process that leads to the progression of SMM to active MM. This review provides a critical description of available data, including risk factors and risk models of progression, as well as clinical trials investigating interventions for this patient population. We describe 2 cases in which patients were seen before the concept of a myeloma-defining event was established. Today, based on the International Myeloma Working Group…

Прогрессивная многофукальная лейкоэнцефалопатия в множестве миеломы.

Прогрессивная многофукальная лейкоэнцефалапатия (ПМЛ) является редкой и часто смертельной болезнью центральной нервной системы, вызванной возобновлением вируса JC в контексте иммунной подавления, такой как ВИЧ, злокачественность и некоторые иммуноводные препараты. О ПМЛ сообщалось лишь редко у нескольких пациентов, страдающих миэломой, и его характерные черты и естественная история этой группы населения не хорошо известны. Мы описываем шесть случаев PML среди многих пациентов миэломы, которые лечились в нашем учреждении в период с 2013 по 2022 год, включая два случая, которые развивались в ход

Совпадение в аннотации оригинала
Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal demyelinating disease of the central nervous system caused by reactivation of the JC virus in the context of immune suppression such as HIV, malignancy, and certain immunomodulatory medications. PML has been reported only rarely in multiple myeloma patients, and its presenting feature…

Anaplastic multiple myeloma with MYC rearrangement.

A 52-year-old man with rapidly progressive paraplegia was presented to us with paravertebral tumors. Laminectomy with tumor resection was performed, and pathological analysis of the tumor revealed compact proliferation of anaplastic plasmacytoid cells. G-band analysis of the tumor revealed a complex karyotype, including IgH/MYC translocation. The patient was diagnosed with anaplastic multiple myeloma (AMM) with MYC arrangement, and cytotoxic chemotherapy followed by autologous hematopoietic stem cell transplantation resulted in long-term disease-free remission. This is the first report describ…

Chromosome 1q21 abnormalities in multiple myeloma.

Gain of chromosome 1q (+1q) is one of the most common recurrent cytogenetic abnormalities in multiple myeloma (MM), occurring in approximately 40% of newly diagnosed cases. Although it is often considered a poor prognostic marker in MM, +1q has not been uniformly adopted as a high-risk cytogenetic abnormality in guidelines. Controversy exists regarding the importance of copy number, as well as whether +1q is itself a driver of poor outcomes or merely a common passenger genetic abnormality in biologically unstable disease. Although the identification of a clear pathogenic mechanism from +1q rem…

ASH Highlights and Commentary: Multiple Myeloma

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… B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches. … Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. …

Extramedullary Multiple Myeloma with Hepatic Involvement.

Hepatic involvement with space-occupying lesions seen in patients with multiple myeloma (MM) is a rare phenomenon. We present two cases of extramedullary multiple myeloma (EMM), with different presentations to highlight the diversity of clinical presentation. Clinically relevant hepatic involvement of myeloma is uncommon and can pose management problems. Hepatic involvement of EMM is indicative of a poor prognosis. Early recognition can help stage and prognosticate the disease.

[Multiple myeloma from the pathologist's perspective].

BACKGROUND: Multiple myeloma (MM) is one of the most common hematological neoplasms and accounts for approximately 1% of human cancers. OBJECTIVES: Description of current diagnostics and classification of MM and related plasma cell neoplasms from the pathology viewpoint. MATERIALS AND METHODS: Current knowledge regarding pathology and genetics of MM is summarized and tissue-based diagnostics following international consensus classifications and the current S3 guideline are described. RESULTS: MM and related neoplasms are composed of malignant plasma cells that secrete a monoclonal immunoglo…

How We Approach Smoldering Multiple Myeloma.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

Совпадение в полном тексте источника
… By the 20/2/20 criteria, this patient has high-risk smoldering multiple myeloma. … Kyle RA Remstein ED Therneau TM et al Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma N Engl J Med 356 2582 2590 2007 17582068 10.1056/NEJMoa070389 6. Landgren O Shall we treat smoldering multiple myeloma in the near future? …

Selinexor in relapsed/refractory multiple myeloma.

Multiple myeloma (MM) represents an incurable hematologic malignancy. Despite significant advances over the past decade, with the advent of multiple new classes of anti-myeloma agents, including immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies, patients ultimately relapse. Selinexor is a first-in-class exportin-1 inhibitor with activity in these multiply relapsed and refractory patients. Although the current Food and Drug Administration (FDA) approval is for the doublet of Selinexor in combination with dexamethasone, ongoing clinical trials are evaluating a number of com…