Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.4
5.2
Journals
Cancers
Special Issues
Preclinical and Clinical Studies of Novel Therapies in Leukemia and...
share announcement

Preclinical and Clinical Studies of Novel Therapies in Leukemia and Lymphoma

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 August 2021) | Viewed by 19869

Special Issue Editor

Prof. Dr. Tadeusz Robak

E-Mail Website
Guest Editor
1. Department of Hematology, Medical University of Lodz, 93-510 Lodz, Poland
2. Department of General Hematology, Copernicus Memorial Hospital, 93-510 Lodz, Poland
Interests: leukemia; lymphoma; multiple myeloma; autoimmune cytopenias; targeted drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the last few years, novel agents have produced unprecedented outcomes in treatment options for patients with leukemias and lymphomas. In this Special Issue of Cancers, we highlight new targeted therapies in leukemias and lymphomas, with an emphasis on targeted drugs and immunotherapy. In hematologic malignancies, we include antibody-based therapies, such as naked monoclonal antibodies, antibody–drug conjugates, and bispecific T-cell engaging (BiTE) antibodies; immune checkpoint therapies; and adoptive cellular therapies, including antigen receptor (CAR) T cells. Apart from the above immunotherapeutic approaches, other targeted therapies improve outcomes of hematological malignancies, including inhibitors of B-cell receptor signaling pathway (BTK and PI3K inhibitors) and the inhibitors of the antiapoptotic protein BCL-2 (venetoclax). Antibody–drug conjugates (ADCs) are also a novel class of drugs which combine the cytotoxic potency of chemotherapy with the selectivity of monoclonal antibody to provide a novel safe and effective therapy. Several ADCs have been studied and are in current clinical practice, including brentuximab vedotin, inotuzumab ozogamicin, and trastuzumab emtansine. In addition, a growing number of next-generation molecules are in clinical trials with a promise of improved efficacy and reduced toxicity. We also emphasize the principles of management of hematologic malignancies in the current era of genomic medicine, with a focus on considerations for targeting mutation-specific vulnerabilities. This issue also highlights unique challenges to the use of novel agents in 2021, including considerations of curative potential.

Prof. Dr. Tadeusz Robak
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 short 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

  • chronic lymphocytic leukemia
  • acute myeloid leukemia
  • acute lymphoblastic leukemia
  • chronic myeloid leukemia
  • non-Hodgkin lymphoma
  • Hodgkin lymphoma
  • monoclonal antibody
  • targeted drugs
  • immunotoxin
  • CAR-T

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

16 pages, 2879 KiB  
Article
PAK4 and NAMPT as Novel Therapeutic Targets in Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Mantle Cell Lymphoma
by Husain Yar Khan, Md. Hafiz Uddin, Suresh Kumar Balasubramanian, Noor Sulaiman, Marium Iqbal, Mahmoud Chaker, Amro Aboukameel, Yiwei Li, William Senapedis, Erkan Baloglu, Ramzi M. Mohammad, Jeffrey Zonder and Asfar S. Azmi
Cancers 2022, 14(1), 160; https://doi.org/10.3390/cancers14010160 - 29 Dec 2021
Cited by 9 | Viewed by 2500
Abstract
Diffuse large B-cell lymphoma (DLBCL), grade 3b follicular lymphoma (FL), and mantle cell lymphoma (MCL) are aggressive non-Hodgkin’s lymphomas (NHL). Cure rates are suboptimal and novel treatment strategies are needed to improve outcomes. Here, we show that p21-activated kinase 4 (PAK4) and nicotinamide [...] Read more.
Diffuse large B-cell lymphoma (DLBCL), grade 3b follicular lymphoma (FL), and mantle cell lymphoma (MCL) are aggressive non-Hodgkin’s lymphomas (NHL). Cure rates are suboptimal and novel treatment strategies are needed to improve outcomes. Here, we show that p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyl transferase (NAMPT) is critical for lymphoma subsistence. Dual targeting of PAK4-NAMPT by the Phase I small molecule KPT-9274 suppressed cell proliferation in DLBCL, FL, and MCL. Growth inhibition was concurrent with apoptosis induction alongside activation of pro-apoptotic proteins and reduced pro-survival markers. We observed NAD suppression, ATP reduction, and consequent cellular metabolic collapse in lymphoma cells due to KPT-9274 treatment. KPT-9274 in combination with standard-of-care chemotherapeutics led to superior inhibition of cell proliferation. In vivo, KPT-9274 could markedly suppress the growth of WSU-DLCL2 (DLBCL), Z-138, and JeKo-1 (MCL) sub-cutaneous xenografts, and a remarkable increase in host life span was shown, with a 50% cure of a systemic WSU-FSCCL (FL) model. Residual tumor analysis confirmed a reduction in total and phosphorylated PAK4 and activation of the pro-apoptotic cascade. This study, using various preclinical experimental models, demonstrates the therapeutic potential of targeting PAK4-NAMPT in DLBCL, FL, and MCL. The orally bioavailable, safe, and efficacious PAK4-NAMPT dual inhibitor KPT-9274 warrants further clinical investigation. Full article
(This article belongs to the Special Issue Preclinical and Clinical Studies of Novel Therapies in Leukemia and Lymphoma)
►▼ Show Figures

Figure 1

9 pages, 964 KiB  
Article
Real World Evidence of CAR T-Cell Therapies for the Treatment of Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma: A Monocentric Experience
by Beatrice Casadei, Lisa Argnani, Serafina Guadagnuolo, Cinzia Pellegrini, Vittorio Stefoni, Alessandro Broccoli, Laura Nanni, Alice Morigi, Ginevra Lolli, Maria Guarino, Luca Spinardi, Elisabetta Pierucci, Stefano Fanti, Michele Bartoletti, Michele Dicataldo, Elena Sabattini, Francesca Bonifazi and Pier Luigi Zinzani
Cancers 2021, 13(19), 4789; https://doi.org/10.3390/cancers13194789 - 24 Sep 2021
Cited by 19 | Viewed by 3545
Abstract
Large B-cell lymphomas (LBCL) are the most common types of non-Hodgkin lymphoma. Although outcomes have improved thanks to the introduction of rituximab-based chemoimmunotherapy, certain LBCL still represents a challenge because of initial resistance to therapy or recurrent relapses. Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel [...] Read more.
Large B-cell lymphomas (LBCL) are the most common types of non-Hodgkin lymphoma. Although outcomes have improved thanks to the introduction of rituximab-based chemoimmunotherapy, certain LBCL still represents a challenge because of initial resistance to therapy or recurrent relapses. Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are second-generation autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapies approved for patients with relapsed/refractory (R/R) LBCL, based on the results of phase II pivotal single-arm trials ZUMA-1 (for axi-cel) and JULIET (for tisa-cel). Here, we report patients outcomes with axi-cel and tisa-cel in the standard of care (SoC) setting for R/R LBCL, treated at our Institution. Data were collected from patients who underwent leukapheresis between August 2019 and February 2021. Toxicities were graded and managed according to the institution’s guidelines. Responses were assessed as per Lugano 2014 classification. Of the 30 patients who underwent leukapheresis, 18 (60%) received axi-cel, while 12 (40%) tisa-cel. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 10% and 16% patients, respectively. Best objective and complete response rates were 73.3% and 40%, respectively. Treatment in SoC setting with CD19 CAR T-cell therapies for R/R LBCL showed a manageable safety profile and high objective response rate. Full article
(This article belongs to the Special Issue Preclinical and Clinical Studies of Novel Therapies in Leukemia and Lymphoma)
►▼ Show Figures

Figure 1

14 pages, 982 KiB  
Article
Poor Neutralizing Antibody Responses in 132 Patients with CLL, NHL and HL after Vaccination against SARS-CoV-2: A Prospective Study
by Evangelos Terpos, Maria Gavriatopoulou, Despina Fotiou, Chara Giatra, Ioannis Asimakopoulos, Maria Dimou, Aimilia D. Sklirou, Ioannis Ntanasis-Stathopoulos, Ismini Darmani, Alexandros Briasoulis, Efstathios Kastritis, Maria Angelopoulou, Ioannis Baltadakis, Panayiotis Panayiotidis, Ioannis P. Trougakos, Theodoros P. Vassilakopoulos, Maria Pagoni and Meletios A. Dimopoulos
Cancers 2021, 13(17), 4480; https://doi.org/10.3390/cancers13174480 - 06 Sep 2021
Cited by 43 | Viewed by 3587
Abstract
Emerging data suggest suboptimal antibody responses to COVID-19 vaccination in patients with hematological malignancies. We evaluated the humoral response following the BNT162b2 vaccine in patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), and Hodgkin’s lymphoma (HL). An FDA-approved, ELISA-based methodology was implemented [...] Read more.
Emerging data suggest suboptimal antibody responses to COVID-19 vaccination in patients with hematological malignancies. We evaluated the humoral response following the BNT162b2 vaccine in patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), and Hodgkin’s lymphoma (HL). An FDA-approved, ELISA-based methodology was implemented to evaluate the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 on day 1 of the first vaccine, and afterwards on day 22 and 50. One hundred and thirty-two patients with CLL/lymphomas and 214 healthy matched controls vaccinated during the same period, at the same center were enrolled in the study (NCT04743388). Vaccination with two doses of the BNT162b2 vaccine led to lower production of NAbs against SARS-CoV-2 in patients with CLL/lymphomas compared with controls both on day 22 and on day 50 (p < 0.001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with Rituximab, Bruton’s tyrosine kinase inhibitors, or chemotherapy was an independent prognostic factor for suboptimal antibody response. Patients with HL showed superior humoral responses to the NHL/CLL subgroups. In conclusion, patients with CLL/lymphomas have low humoral response following COVID-19 vaccination, underlining the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures. Full article
(This article belongs to the Special Issue Preclinical and Clinical Studies of Novel Therapies in Leukemia and Lymphoma)
►▼ Show Figures

Figure 1

16 pages, 1102 KiB  
Article
Cladribine Combined with Low-Dose Cytarabine as Frontline Treatment for Unfit Elderly Acute Myeloid Leukemia Patients: Results from a Prospective Multicenter Study of Polish Adult Leukemia Group (PALG)
by Bożena Katarzyna Budziszewska, Aleksander Salomon-Perzyński, Katarzyna Pruszczyk, Joanna Barankiewicz, Agnieszka Pluta, Grzegorz Helbig, Anna Janowska, Marta Kuydowicz, Łukasz Bołkun, Jarosław Piszcz, Elżbieta Patkowska, Marzena Wątek, Piotr Małecki, Sylwia Kościołek-Zgódka, Edyta Cichocka, Grzegorz Charliński, Anna Irga-Staniukiewicz, Jan Maciej Zaucha, Agnieszka Piekarska, Tomasz Gromek, Marek Hus, Karol Wójcik, Małgorzata Raźny, Mariola Sędzimirska, Bartosz Puła, Sebastian Giebel, Sebastian Grosicki, Agnieszka Wierzbowska and Ewa Lech-Marańdaadd Show full author list remove Hide full author list
Cancers 2021, 13(16), 4189; https://doi.org/10.3390/cancers13164189 - 20 Aug 2021
Cited by 5 | Viewed by 2503
Abstract
Acute myeloid leukemia (AML) in older unfit patients is a therapeutic challenge for clinical hematologists. We evaluated the efficacy and safety of a novel low-intensity regimen consisting of low-dose cytarabine and cladribine (LD-AC+cladribine) in first-line treatment of elderly (≥60 years) AML patients not [...] Read more.
Acute myeloid leukemia (AML) in older unfit patients is a therapeutic challenge for clinical hematologists. We evaluated the efficacy and safety of a novel low-intensity regimen consisting of low-dose cytarabine and cladribine (LD-AC+cladribine) in first-line treatment of elderly (≥60 years) AML patients not eligible for intensive chemotherapy (IC) who had either the Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 or the hematopoietic cell transplantation comorbidity index (HCT-CI) score ≥3. The induction phase included two cycles of LD-AC+cladribine. Patients who achieved at least partial remission (PR) received maintenance treatment with LD-AC alone. Overall, 117 patients with a median age of 70 years were enrolled. Adverse cytogenetics, ECOG PS ≥2 and HCT-CI score ≥3 was observed in 43.5%, 60%, and 58% of patients, respectively. The response rate (≥PR) was 54% (complete remission [CR], 32%; CR with incomplete hematologic recovery [CRi], 5%). A median overall survival (OS) was 21 and 8.8 months in CR/CRi and PR group, respectively. Advanced age (≥75 years) and adverse cytogenetics had a negative impact on OS. The 56-day mortality rate was 20.5%. In conclusion, LD-AC+cladribine is a beneficial therapeutic option with a predictable safety profile in elderly AML patients not eligible for IC. Full article
(This article belongs to the Special Issue Preclinical and Clinical Studies of Novel Therapies in Leukemia and Lymphoma)
►▼ Show Figures

Figure 1

Review

Jump to: Research

14 pages, 11247 KiB  
Review
Richter Transformation in Chronic Lymphocytic Leukemia: Update in the Era of Novel Agents
by Tamar Tadmor and Ilana Levy
Cancers 2021, 13(20), 5141; https://doi.org/10.3390/cancers13205141 - 14 Oct 2021
Cited by 15 | Viewed by 6986
Abstract
Richter transformation (RT) is a poorly understood complication of chronic lymphocytic leukemia (CLL) with a dismal prognosis. It is associated with a switch in histopathology and biology, generally with a transformation of the original CLL clone to diffuse large B-cell lymphoma (DLBCL) or [...] Read more.
Richter transformation (RT) is a poorly understood complication of chronic lymphocytic leukemia (CLL) with a dismal prognosis. It is associated with a switch in histopathology and biology, generally with a transformation of the original CLL clone to diffuse large B-cell lymphoma (DLBCL) or less frequently to Hodgkin’s variant of Richter transformation (HVRT). It occurs in 2–10% of CLL patients, with an incidence rate of 0.5–1% per year, and may develop in treatment-naïve patients, although it is more common following therapy. In recent years, there has been a deeper understanding of the molecular pathogenesis of RT that involves the inactivation of the TP53 tumor suppressor gene in 50–60% of cases and the activation of aberrations of NOTCH1 and MYC pathways in about 30% of cases. Compared to the preceding CLL, 80% of cases with DLBCL-RT and 30% of HVRT harbor the same IGHV-D-J rearrangements, indicating a clonal evolution of the disease, while the remaining cases represent de novo lymphomas that are clonally unrelated. Despite advances in understanding the molecular variations and the pathogenesis of the disease, there is still no significant improvement in patient outcomes. However, if no clinical trials were designed for patients with RT in the past, now there many studies for these patients that incorporate new drugs and novel combinations that are being explored. In this review, we summarize the new information accumulated on RT with special emphasis on results involving the novel therapy tested for this entity, which represents an unmet clinical need. Full article
(This article belongs to the Special Issue Preclinical and Clinical Studies of Novel Therapies in Leukemia and Lymphoma)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop