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 3448

Special Issue Editor


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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

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Keywords

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

Published Papers (3 papers)

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Research

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
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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 1561
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
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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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