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Cancers
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CAR T Cells in Lymphoma and Multiple Myeloma
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CAR T Cells in Lymphoma and Multiple Myeloma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 January 2025) | Viewed by 4230

Special Issue Editors

Dr. Javier Munoz

E-Mail Website
Guest Editor
Division of Hematology, Medical Oncology, Mayo Clinic, Phoenix, AZ 85054, USA
Interests: lymphoma; cellular therapies; CAR T cells
Dr. Julia Erin Wiedmeier-Nutor

E-Mail Website
Guest Editor
Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ 85054, USA
Interests: multiple myeloma; cellular therapies; dysproteinemia

Special Issue Information

Dear Colleagues,

Cellular therapies, including chimeric antigen receptor (CAR) T cell therapy and bispecific antibodies (BiTE), have changed the treatment landscape for lymphomas and multiple myeloma. These treatments are primarily used in the relapsed or refractory setting, although exploration in early lines of therapy is under investigation in clinical trials. Despite exciting outcomes, there are a number of challenges that remain. Examples include poor T cell expansion and short-term T cell persistence, leading to suboptimal response and/or relapse. The purpose of this Special Issue is to understand how to decrease the toxicity and increase the efficacy of CAR T cell therapy in patients with lymphoma or multiple myeloma.

Dr. Javier Munoz
Dr. Julia Erin Wiedmeier-Nutor
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • multiple myeloma
  • lymphoma
  • CAR T therapy
  • bi-specific antibodies
  • cellular therapy

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Published Papers (3 papers)

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Review

17 pages, 887 KiB  
Review
The Role of the Tumor Microenvironment in T-Cell Redirecting Therapies of Large B-Cell Lymphoma: Lessons Learned from CAR-T to Bispecific Antibodies
by Kirill V. Lepik and Vladislav V. Markelov
Cancers 2025, 17(2), 317; https://doi.org/10.3390/cancers17020317 - 20 Jan 2025
Viewed by 733
Abstract
T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-Ts) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for the optimization of their use with combination or [...] Read more.
T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-Ts) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for the optimization of their use with combination or consolidation strategies, which necessitates the prognostic stratification of patients. While traditional clinical prognostic factors identified in the era of chemotherapy are characterized by limited value, the tumor microenvironment (TME) is becoming a new prognostic cluster. We examine how the heterogeneity of LBCL, characterized by variations in tumor parameters and differences in TME immune cell composition, immune checkpoint expression, and cytokine milieu, correlates with both positive responses and resistance to treatment. While classical parameters such as histological subtype, cell of origin, and target antigen expression lack proven prognostic value for T-cell redirecting therapies, the density and functional state of tumor-infiltrating lymphocytes, tumor-associated macrophages, and immune checkpoint molecules are shown to be critical determinants of therapeutic success, particularly in CAR-T therapy. We identify several gaps in the current knowledge and suggest that the insights gained from CAR-T experience could be instrumental in refining BSA applications. This report also highlights limitations in the current knowledge, as TME data derive from a limited number of registrational trials with varying methodologies, complicating cross-study comparisons and often focusing on immediate response metrics rather than long-term outcomes. By dissecting the complex interactions within the TME, this review aims to identify new prognostic factors and targets, ultimately fostering more effective and tailored treatment strategies for LBCL patients. Full article
(This article belongs to the Special Issue CAR T Cells in Lymphoma and Multiple Myeloma)
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21 pages, 991 KiB  
Review
Measurable Residual Disease Testing in Multiple Myeloma Following T-Cell Redirecting Therapies
by Kevin Guanwen Shim and Rafael Fonseca
Cancers 2024, 16(19), 3288; https://doi.org/10.3390/cancers16193288 - 27 Sep 2024
Cited by 1 | Viewed by 1384
Abstract
Several novel T-cell-based therapies have recently become available for multiple myeloma (MM). These T-cell redirecting therapies (TRTs) include chimeric antigen receptor T-cells (CAR-T) and bispecific antibodies (BiAbs). In both clinical trial and real-world data, these therapies have demonstrated high rates of deep clinical [...] Read more.
Several novel T-cell-based therapies have recently become available for multiple myeloma (MM). These T-cell redirecting therapies (TRTs) include chimeric antigen receptor T-cells (CAR-T) and bispecific antibodies (BiAbs). In both clinical trial and real-world data, these therapies have demonstrated high rates of deep clinical response, and some are now approved for second-line treatment for relapsed MM. The deep and sustained clinical responses these therapies are capable of inducing will require sophisticated response monitoring to provide meaningful information for patient care. Obtaining measurable residual disease (MRD) negativity has been validated as an independent positive prognostic marker for progression-free survival (PFS) and overall survival (OS) in both newly diagnosed and relapsed refractory patients with multiple myeloma. Assessment for MRD negativity was performed in all of the trials for FDA-approved TRT. Here, we summarize pertinent data for MRD assessment following TRT in MM and provide a rationale and structured framework for conducting MRD testing post TRT. Full article
(This article belongs to the Special Issue CAR T Cells in Lymphoma and Multiple Myeloma)
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Figure 1

19 pages, 303 KiB  
Review
Circulating Tumor DNA as a Complementary Prognostic Biomarker during CAR-T Therapy in B-Cell Non-Hodgkin Lymphomas
by Sarah Monick and Allison Rosenthal
Cancers 2024, 16(10), 1881; https://doi.org/10.3390/cancers16101881 - 15 May 2024
Cited by 4 | Viewed by 1611
Abstract
The emergence of CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment paradigm for R/R B-cell NHLs. However, challenges persist in accurately evaluating treatment response and detecting early relapse, necessitating the exploration of novel biomarkers. Circulating tumor DNA (ctDNA) via liquid [...] Read more.
The emergence of CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment paradigm for R/R B-cell NHLs. However, challenges persist in accurately evaluating treatment response and detecting early relapse, necessitating the exploration of novel biomarkers. Circulating tumor DNA (ctDNA) via liquid biopsy is a non-invasive tool for monitoring therapy efficacy and predicting treatment outcomes in B-NHL following CAR-T therapy. By overcoming the limitations of conventional imaging modalities, ctDNA assessments offer valuable insights into response dynamics, molecular mechanisms of resistance, and early detection of molecular relapse. Integration of ctDNA monitoring into clinical practice holds promise for personalized therapeutic strategies, guiding the development of novel targeted therapies, and enhancing patient outcomes. However, standardization of assay methodologies and consensus on clinical response metrics are imperative to unlock the full potential of ctDNA in the management of B-NHL. Prospective validation of ctDNA in clinical trials is necessary to establish its role as a complementary decision aid. Full article
(This article belongs to the Special Issue CAR T Cells in Lymphoma and Multiple Myeloma)
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