Treatment horizon in multiple myeloma

Soekojo, Cinnie Yentia; Chng, Wee Joo

doi:10.1111/ejh.13840

Cited by 18 publications

(10 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One such approach is ASI, which has been developed and shown to significantly enhance treatment outcomes in MM patients. [41,42] Various forms of ASI have been approved for clinical use, including monoclonal antibodies (e.g., daratumumab, anti-CD83 monoclonal antibody), bispecific T-cell engagers (e.g., teclistamab), and BCMA-directed CAR T-cell therapy (e.g., idacabtagene vicleucel, clitacabtagene autoleucel), [41,42] indicating the potential of ASI as a treatment modality for MM. Among the ASI strategies, inducing cancer-specific CTLs using immunogenic peptides derived from well-characterized tumor-associated antigens provides a novel platform for therapeutic cancer vaccines.…”

Section: Discussionmentioning

confidence: 99%

Identification of HLA‐restricted Cytotoxic T Lymphocyte Epitopes of B Cell Maturation Antigen as Promising Peptide Vaccine Candidates for Preventive and Therapeutic Strategies in Multiple Myeloma

Chiraphapphaiboon,

Luangwattananun,

Chieochansin

et al. 2023

Advanced Therapeutics

View full text Add to dashboard Cite

Multiple myeloma (MM) is an incurable hematologic malignancy for which curative treatment remains elusive. Consequently, immunotherapeutic strategies that selectively induce MM‐specific T cell responses by targeting MM‐associated antigens have emerged. This study aims to identify HLA‐restricted cytotoxic T lymphocyte (CTL) epitopes derived from B cell maturation antigen (BCMA) as potential peptide vaccine candidates to advance preventive and therapeutic interventions for MM. BCMA expression in bone marrow tissue samples from 96.8% of MM patients is observed, and the positive membrane BCMA expression is associated with inferior overall survival outcomes. Through an in silico model, four BCMA epitope peptides that exhibit in vitro concentration‐dependent binding to the HLA*A11:01 molecule are identified. Comparative analyses reveal that BCMA‐specific CTLs stimulated by BCMA‐2, BCMA‐3, and BCMA‐4 peptides exhibit significantly greater cytolysis of cancer cells, including BCMA‐overexpressing KMS‐20 and KKU‐055 cells, in comparison to an unpulsed condition or an irrelevant control peptide derived from human immunodeficiency virus‐1 (HIV‐1). Moreover, the observed cytolytic activities of these CTLs are significantly distinct when compared to corresponding BCMA‐negative cells, thereby indicating antigen‐specificity. This study highlights the promising potential of utilizing immunogenic HLA‐A*11:01‐restricted BCMA peptides as a viable approach for cancer vaccination and T cell‐based therapy in the context of MM.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of HLA‐restricted Cytotoxic T Lymphocyte Epitopes of B Cell Maturation Antigen as Promising Peptide Vaccine Candidates for Preventive and Therapeutic Strategies in Multiple Myeloma

Chiraphapphaiboon,

Luangwattananun,

Chieochansin

et al. 2023

Advanced Therapeutics

View full text Add to dashboard Cite

show abstract

“…The growing number of treatment options, for both newly diagnosed and relapsed/refractory cases, has made the clinical landscape increasingly complex ( 7 ). With various new therapeutic options being studied, the landscape is expected to continuously evolve ( 6 ). Consequently, a MMDT must be constructed in a modular way, so that it can be easily updated and validated to stay up-to-date to the fast-changing clinical landscape.…”

Section: Resultsmentioning

confidence: 99%

“…It involves deciding which drugs to use, when to use them, and whether they should be administered in a specific order or combined together ( 1 ). Established and novel regimens are multifaceted and include alkylators, steroids, proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), histone deacetylase inhibitors (HDACi), monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), chimeric antigen-T-cell therapy (CAR-T), peptide-drug conjugates, selective inhibitors of nuclear export (SINEs) and small-molecule targeted therapy ( 5 , 6 ). These agents are either used as single therapies or can be combined to doublet, triplet or quadruplet regimens and can be used as induction before autologous stem cell transplantation (ASCT), as continuous treatment or at the time of relapse ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

A digital twin model for evidence-based clinical decision support in multiple myeloma treatment

Grieb,

Schmierer,

Kim

et al. 2023

Front. Digit. Health

View full text Add to dashboard Cite

The treatment landscape for multiple myeloma (MM) has experienced substantial progress over the last decade. Despite the efficacy of new substances, patient responses tend to still be highly unpredictable. With increasing cognitive burden that is introduced through a complex and evolving treatment landscape, data-driven assistance tools are becoming more and more popular. Model-based approaches, such as digital twins (DT), enable simulation of probable responses to a set of input parameters based on retrospective observations. In the context of treatment decision-support, those mechanisms serve the goal to predict therapeutic outcomes to distinguish a favorable option from a potential failure. In the present work, we propose a similarity-based multiple myeloma digital twin (MMDT) that emphasizes explainability and interpretability in treatment outcome evaluation. We've conducted a requirement specification process using scientific literature from the medical and methodological domains to derive an architectural blueprint for the design and implementation of the MMDT. In a subsequent stage, we've implemented a four-layer concept where for each layer, we describe the utilized implementation procedure and interfaces to the surrounding DT environment. We further specify our solutions regarding the adoption of multi-line treatment strategies, the integration of external evidence and knowledge, as well as mechanisms to enable transparency in the data processing logic. Furthermore, we define an initial evaluation scenario in the context of patient characterization and treatment outcome simulation as an exemplary use case for our MMDT. Our derived MMDT instance is defined by 475 unique entities connected through 438 edges to form a MM knowledge graph. Using the MMRF CoMMpass real-world evidence database and a sample MM case, we processed a complete outcome assessment. The output shows a valid selection of potential treatment strategies for the integrated medical case and highlights the potential of the MMDT to be used for such applications. DT models face significant challenges in development, including availability of clinical data to algorithmically derive clinical decision support, as well as trustworthiness of the evaluated treatment options. We propose a collaborative approach that mitigates the regulatory and ethical concerns that are broadly discussed when automated decision-making tools are to be included into clinical routine.

show abstract

“…In the therapeutic scenario of MM, there are different approaches built on the biological characteristics of the disease and patient characteristics such as comorbidity, age and performance status. To date, daratumumab, bortezomib, dexamethasone and immunomodulators such as thalidomide and lenalidomide used in combination are the first line of treatment for newly diagnosed transplant-eligible patients [ 115 ].…”

Section: Role Of Multiple Myeloma Therapy In Autoimmune Diseasesmentioning

confidence: 99%

Autoimmune Diseases and Plasma Cells Dyscrasias: Pathogenetic, Molecular and Prognostic Correlations

Giordano,

Cacciola,

Barone

et al. 2024

Diagnostics

View full text Add to dashboard Cite

Multiple myeloma and monoclonal gammopathy of undetermined significance are plasma cell dyscrasias characterized by monoclonal proliferation of pathological plasma cells with uncontrolled production of immunoglobulins. Autoimmune pathologies are conditions in which T and B lymphocytes develop a tendency to activate towards self-antigens in the absence of exogenous triggers. The aim of our review is to show the possible correlations between the two pathological aspects. Molecular studies have shown how different cytokines that either cause inflammation or control the immune system play a part in the growth of immunotolerance conditions that make it easier for the development of neoplastic malignancies. Uncontrolled immune activation resulting in chronic inflammation is also known to be at the basis of the evolution toward neoplastic pathologies, as well as multiple myeloma. Another point is the impact that myeloma-specific therapies have on the course of concomitant autoimmune diseases. Indeed, cases have been observed of patients suffering from multiple myeloma treated with daratumumab and bortezomib who also benefited from their autoimmune condition or patients under treatment with immunomodulators in which there has been an arising or worsening of autoimmunity conditions. The role of bone marrow transplantation in the course of concomitant autoimmune diseases remains under analysis.

show abstract

Treatment horizon in multiple myeloma

Cited by 18 publications

References 122 publications

Identification of HLA‐restricted Cytotoxic T Lymphocyte Epitopes of B Cell Maturation Antigen as Promising Peptide Vaccine Candidates for Preventive and Therapeutic Strategies in Multiple Myeloma

Identification of HLA‐restricted Cytotoxic T Lymphocyte Epitopes of B Cell Maturation Antigen as Promising Peptide Vaccine Candidates for Preventive and Therapeutic Strategies in Multiple Myeloma

A digital twin model for evidence-based clinical decision support in multiple myeloma treatment

Autoimmune Diseases and Plasma Cells Dyscrasias: Pathogenetic, Molecular and Prognostic Correlations

Contact Info

Product

Resources

About