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Cancers
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Immunotherapy in the Management of Hematologic Malignancy
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Immunotherapy in the Management of Hematologic Malignancy

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

Deadline for manuscript submissions: 30 November 2024 | Viewed by 8633

Special Issue Editor

Dr. Mohammad S. Hossain

E-Mail Website
Guest Editor
Department of Hematology & Medical Oncology, Winship Cancer Institute, School of Medicine, Emory University, Atlanta, GA 30322, USA
Interests: basic and cellular immunology; cellular and cytokines immunotherapies; allo/auto HSCT; GvHD; viral infection; autoimmune diseases; clinical research

Special Issue Information

Dear Colleagues,

Hematologic malignancies are heterogeneous groups of diseases that include Hodgkin and non-Hodgkin lymphoma, multiple myeloma and plasma cell dyscrasias, acute and chronic leukemia, and myelodysplasia. Each year more than a million people die from hematologic malignancies around the world due to lack of effective therapies. While conventional chemotherapy and high-dose chemotherapy followed by autologous or allogeneic hematopoietic stem cell transplantation have shown significant clinical activity in the management of patients with hematological malignancies, chemotherapy-induced toxicities, including cytopenia and opportunistic infections, as well as transplant-specific toxicities such as donor T-cell-mediated graft-vs-host disease (GvHD), represent life-threatening complications that limit the application of these approaches to younger and healthier patients. New treatment strategies based upon immunotherapy are now showing promise in treating patients whose disease has relapsed after conventional chemotherapy.  The failure of innate immunity (NK, macrophages, etc) and adaptive immunity (CD4+ and CD8+ T-cells) is believed to be responsible for the development of clinically detectable hematological malignancies. Therefore, novel treatment strategies that stimulate the immune system to attack newly generated cancer cells are the primary basis of novel immunotherapy treatments.

Several types of immunotherapy that have been found to be clinically useful include: (1) cytokines therapy (IL-2, interferons, GMCSF, IL-12, etc.); (2) therapies based on humanized monoclonal antibodies (Afutuzumab targeting CD20 expressing lymphoma, Apolizumab targeting HLA-DR expressing hematological cancer cells, etc); (3) monoclonal antibodies that prevent T-cell tolerance (PD-1, PD-L1, CTLA-4, etc.); and (4) adoptive T-cell therapy engineered to express chimeric antigen receptors (CARs) targeting selective tumors.

Dr. Mohammad S. Hossain
Guest Editor

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

  • allo/auto HSCT
  • GvHD
  • immunotherapy
  • viral infection
  • hematologic malignancy

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Published Papers (6 papers)

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Research

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19 pages, 2887 KiB  
Article
Expression of mGluR5 in Pediatric Hodgkin and Non-Hodgkin lymphoma—A Comparative Analysis of Immunohistochemical and Clinical Findings Regarding the Association between Tumor and Paraneoplastic Neurological Disease
by Ingeborg Viezens, Ellen Knierim, Hedwig E. Deubzer, Kathrin Hauptmann, Jessica Fassbender, Susanne Morales-Gonzalez, Angela M. Kaindl, Markus Schuelke and Marc Nikolaus
Cancers 2024, 16(13), 2452; https://doi.org/10.3390/cancers16132452 - 4 Jul 2024
Viewed by 2034
Abstract
Autoantibodies targeting the neuronal antigen metabotropic glutamate receptor 5 (mGluR5) have been identified in patients with Ophelia syndrome, which describes a co-occurrence of paraneoplastic limbic encephalitis and Hodgkin lymphoma (HL). Little data exist regarding frequency and function of mGluR5 in HL and its [...] Read more.
Autoantibodies targeting the neuronal antigen metabotropic glutamate receptor 5 (mGluR5) have been identified in patients with Ophelia syndrome, which describes a co-occurrence of paraneoplastic limbic encephalitis and Hodgkin lymphoma (HL). Little data exist regarding frequency and function of mGluR5 in HL and its potential role in causing seropositive paraneoplastic disease. We studied a representative cohort of pediatric HL and NHL patients (n = 57) using immunohistochemistry and fluorescence staining to investigate mGluR5 expression. All lymphoma tissues displayed positive mGluR5 staining, with focus on Hodgkin–Reed–Sternberg (H-RS) cells. We did not detect any mGluR5 staining in tumor-free lymph nodes, which is consistent with the absence of GRM5 transcripts in RNA-sequencing data from non-malignant B and T cells. The frequent presence in pediatric lymphoma falls in line with reports of mGluR5 expression and associated tumor progression in other malignancies. We tested for correlation with clinical features, focusing on disease progression and neurological symptoms. Low mGluR5 expression in H-RS cells correlated with young patient age (<15 years) and positive histology for EBV infection. Paraneoplastic or neurological symptoms were found exclusively in HL patients. While an impact of mGluR5 on HL severity remains possible, a prognostic value of mGluR5 expression levels requires further investigation. Full article
(This article belongs to the Special Issue Immunotherapy in the Management of Hematologic Malignancy)
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9 pages, 563 KiB  
Communication
Adverse Reactions in Relapsed/Refractory B-Cell Lymphoma Administered with Chimeric Antigen Receptor T Cell Alone or in Combination with Autologous Stem Cell Transplantation
by Haolong Lin, Ting Deng, Lijun Jiang, Fankai Meng, Yang Cao, Yicheng Zhang, Renying Ge and Xiaojian Zhu
Cancers 2024, 16(9), 1722; https://doi.org/10.3390/cancers16091722 - 28 Apr 2024
Viewed by 946
Abstract
(1) Background: The combination of CAR-T with ASCT has been observed to enhance the efficacy of CAR-T cell therapy. However, the impact of this combination on adverse reactions is still uncertain. (2) Methods: Between January 2019 and February 2023, 292 patients diagnosed with [...] Read more.
(1) Background: The combination of CAR-T with ASCT has been observed to enhance the efficacy of CAR-T cell therapy. However, the impact of this combination on adverse reactions is still uncertain. (2) Methods: Between January 2019 and February 2023, 292 patients diagnosed with r/r B-cell lymphoma received either CAR-T therapy alone or in combination with ASCT at our institution. We evaluated the incidence of CRS and CRES and utilized a logistic regression model to identify factors contributing to severe CRS (grade 3–4) and CRES (grade 3–4). (3) Results: The overall incidence of CRS and CRES was 78.9% and 8.2% in 147 patients receiving CAR-T alone, and 95.9% and 15.2% in 145 patients receiving CAR-T combined with ASCT, respectively. The incidence of overall CRS (p < 0.0001) and mild CRS (grade 1–2) (p = 0.021) was elevated in the ASCT combined with CAR-T group. No significant difference was observed in severe CRS and CRES between the groups. Among the 26 cases of lymphoma involving the central nervous system (CNS), 96.2% (25/26) developed CRS (15.4% grade 3–4), and 34.6% (9/26) manifested CRES (7.7% grade 3–4). Female patients had a lower incidence of severe CRS but a higher incidence of severe CRES. Lymphomas with CNS involvement demonstrated a higher risk of CRES compared to those without central involvement. (4) Conclusions: The combination of ASCT with CAR-T demonstrated a preferable option in r/r B-cell lymphoma without an increased incidence of severe CRS and CRES. Full article
(This article belongs to the Special Issue Immunotherapy in the Management of Hematologic Malignancy)
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18 pages, 2391 KiB  
Article
Patient-Reported Outcomes among Multiple Myeloma Patients Treated with Standard of Care Idecabtagene Vicleucel
by Laura B. Oswald, Lisa M. Gudenkauf, Xiaoyin Li, Gabriel De Avila, Lauren C. Peres, Kedar Kirtane, Brian D. Gonzalez, Aasha I. Hoogland, Oanh Nguyen, Yvelise Rodriguez, Rachid C. Baz, Kenneth H. Shain, Melissa Alsina, Frederick L. Locke, Ciara Freeman, Omar Castaneda Puglianini, Taiga Nishihori, Hien Liu, Brandon Blue, Ariel Grajales-Cruz, Heather S. L. Jim and Doris K. Hansenadd Show full author list remove Hide full author list
Cancers 2023, 15(19), 4711; https://doi.org/10.3390/cancers15194711 - 25 Sep 2023
Cited by 2 | Viewed by 2057
Abstract
Idecabtagene vicleucel (ide-cel) was the first FDA-approved chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma (RRMM) patients. This was the first study to evaluate patient-reported outcomes (PROs) among RRMM patients receiving ide-cel in standard of care (SOC). We prospectively assessed health-related quality [...] Read more.
Idecabtagene vicleucel (ide-cel) was the first FDA-approved chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma (RRMM) patients. This was the first study to evaluate patient-reported outcomes (PROs) among RRMM patients receiving ide-cel in standard of care (SOC). We prospectively assessed health-related quality of life (HRQOL) and symptoms from pre-infusion (baseline) through day (D)90 post-infusion. Baseline PRO associations with patient characteristics, mean PRO changes, and time to stable change were evaluated with t-tests, linear mixed-effects models, and Kaplan–Meier analyses, respectively. Within-person change scores and minimally important difference thresholds determined clinical and meaningful significance. Participants (n = 42) were a median of 66 years old (range: 43–81). At baseline, extramedullary disease was associated with worse physical well-being (p = 0.008), global pain (p < 0.001), performance status (p = 0.002), and overall symptom burden (p < 0.001). Fatigue (p < 0.001) and functional well-being (p = 0.003) worsened by D7 before returning to baseline levels. Overall HRQOL (p = 0.008) and physical well-being (p < 0.001) improved by D60. Most participants reported PRO improvement (10–57%) or maintenance (23–69%) by D90. The median time it took to stabile deterioration in functional well-being was 14 days. The median time it took to stabile improvement in physical and emotional well-being was 60 days. Overall, RRMM patients reported improvements or maintenance of HRQOL and symptom burden after SOC ide-cel. Full article
(This article belongs to the Special Issue Immunotherapy in the Management of Hematologic Malignancy)
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20 pages, 3114 KiB  
Article
The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients
by Lukasz Bolkun, Marlena Tynecka, Alicja Walewska, Malgorzata Bernatowicz, Jaroslaw Piszcz, Edyta Cichocka, Tomasz Wandtke, Magdalena Czemerska, Agnieszka Wierzbowska, Marcin Moniuszko, Kamil Grubczak and Andrzej Eljaszewicz
Cancers 2023, 15(18), 4487; https://doi.org/10.3390/cancers15184487 - 9 Sep 2023
Viewed by 1152
Abstract
The development of novel drugs with different mechanisms of action has dramatically changed the treatment landscape of AML patients in recent years. Considering a significant dysregulation of the immune system, inhibitors of immune checkpoint (ICI) proteins provide a substantial therapeutic option for those [...] Read more.
The development of novel drugs with different mechanisms of action has dramatically changed the treatment landscape of AML patients in recent years. Considering a significant dysregulation of the immune system, inhibitors of immune checkpoint (ICI) proteins provide a substantial therapeutic option for those subjects. However, use of ICI in haematological malignancies remains very limited, in contrast to their wide use in solid tumours. Here, we analysed expression patterns of the most promising selected checkpoint-based therapeutic targets in AML patients. Peripheral blood of 72 untreated AML patients was used for flow cytometric analysis. Expression of PD-1, PD-L1, CTLA-4, and B7-H3 was assessed within CD4+ (Th) lymphocytes and CD33+ blast cells. Patients were stratified based on therapy outcome and cytogenetic molecular risk. AML non-responders (NR) showed a higher frequency of PD-1 in Th cells compared to those with complete remission (CR). Reduced blast cell level of CTLA-4 was another factor differentiating CR from NR subjects. Elevated levels of PD-1 were associated with a trend for poorer patients’ survival. Additionally, prognosis for AML patients was worse in case of a higher frequency of B7-H3 in Th lymphocytes. In summary, we showed the significance of selected ICI as outcome predictors in AML management. Further, multicentre studies are required for validation of those data. Full article
(This article belongs to the Special Issue Immunotherapy in the Management of Hematologic Malignancy)
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Review

Jump to: Research

20 pages, 850 KiB  
Review
Breaking Boundaries: Immunotherapy for Myeloid Malignancies
by Tatyana Gavrilova, Eduard Schulz and Alain Mina
Cancers 2024, 16(16), 2780; https://doi.org/10.3390/cancers16162780 - 6 Aug 2024
Viewed by 363
Abstract
Immunotherapy has revolutionized the treatment of myeloid oncologic diseases, particularly for patients resistant to chemotherapy or ineligible for allogeneic stem cell transplantation due to age or fitness constraints. As our understanding of the immunopathogenesis of myeloid malignancies expands, so too do the treatment [...] Read more.
Immunotherapy has revolutionized the treatment of myeloid oncologic diseases, particularly for patients resistant to chemotherapy or ineligible for allogeneic stem cell transplantation due to age or fitness constraints. As our understanding of the immunopathogenesis of myeloid malignancies expands, so too do the treatment options available to patients. Immunotherapy in myeloid malignancies, however, faces numerous challenges due to the dynamic nature of the disease, immune dysregulation, and the development of immune evasion mechanisms. This review outlines the progress made in the field of immunotherapy for myeloid malignancies, addresses its challenges, and provides insights into future directions in the field. Full article
(This article belongs to the Special Issue Immunotherapy in the Management of Hematologic Malignancy)
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24 pages, 348 KiB  
Review
Bispecific Antibodies for the Management of Relapsed/Refractory Multiple Myeloma
by Paola Tacchetti, Simona Barbato, Katia Mancuso, Elena Zamagni and Michele Cavo
Cancers 2024, 16(13), 2337; https://doi.org/10.3390/cancers16132337 - 26 Jun 2024
Viewed by 1474
Abstract
Bispecific antibodies (BsAbs) are artificially engineered antibodies that can bind simultaneously to the CD3 subunit within the T-cell receptor complex and an antigen on tumor cells, leading to T-cell activation and tumor cell killing. BsAbs against BCMA or GPRC5D have shown impressive clinical [...] Read more.
Bispecific antibodies (BsAbs) are artificially engineered antibodies that can bind simultaneously to the CD3 subunit within the T-cell receptor complex and an antigen on tumor cells, leading to T-cell activation and tumor cell killing. BsAbs against BCMA or GPRC5D have shown impressive clinical activity in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), with some agents having already received regulatory approval after the third (by the European Medicines Agency, EMA) or fourth (by the Food and Drug Administration, FDA) line of therapy; the results of early-phase clinical trials targeting FcRH5 are also promising. Overall, BsAbs as monotherapy correlated with an ORR that exceeded 60%, with a high CR rate ranging between 25% and 50% and a median PFS of around 1 year among patients with a median of 4–6 prior lines of therapy. The main toxicities include cytokine release syndrome, cytopenias, hypogammaglobulinemia, and infections; on-target off-tumor adverse events involving the skin, mucosa, hair, and nails may also occur with anti-GPRC5D BsAbs. Active research to increase their efficacy and improve their tolerance is still in progress, including combination therapies and application in earlier treatment lines and the development of novel agents. A better understanding of the mechanisms of resistance is a challenge and could lead to more personalized approaches. Full article
(This article belongs to the Special Issue Immunotherapy in the Management of Hematologic Malignancy)
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