Venetoclax in association with decitabine as effective bridge to transplant in a case of relapsed early T‐cell lymphoblastic leukemia

Zappone, Elisabetta; Cencini, Emanuele; Defina, Marzia; Sicuranza, Anna; Gozzetti, Alessandro; Ciofini, Sara; Raspadori, Donatella; Mecacci, Bianca; Bocchia, Monica

doi:10.1002/ccr3.3041

Cited by 18 publications

(9 citation statements)

References 14 publications

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“…A higher white blood cells (WBC) count at diagnosis (reflecting an elevated tumor burden), an older age and comorbidities (related to a reduced treatment tolerability) are recognized as prognostic factors for a lower complete remission (CR) and shorter duration of response (DOR) [ 44 ]. However, many other immunophenotypic, cytogenetic and molecular disease-related factors have been studied and there is a growing interest about a possible prognostic relevance of an immunosuppressive microenvironment [ 45 , 46 , 47 , 48 ].…”

Section: Tam Role In Leukemiamentioning

confidence: 99%

The Role of Tumor-Associated Macrophages in Hematologic Malignancies

Cencini

Fabbri

Sicuranza

et al. 2021

Cancers

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The tumor microenvironment includes dendritic cells, T-cytotoxic, T-helper, reactive B-lymphoid cells and macrophages; these reactive cells could interplay with malignant cells and promote tumor growth and survival. Among its cellular components, tumor-associated macrophages (TAM) represent a component of the innate immune system and play an important role, especially in hematologic malignancies. Depending on the stimuli that trigger their activation, TAM are polarized towards form M1, contributing to antitumor responses, or M2, associated with tumor progression. Many studies demonstrated a correlation between TAM, disease progression and the patient’s outcome in lymphoproliferative neoplasms, such as Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), even if with conflicting results. A critical hurdle to overcome is surely represented by the heterogeneity in the choice of the optimal markers and methods used for TAM analysis (gene-expression profile vs. immunohistochemistry, CD163vs. CD68vs. CD163/CD68 double-positive cells). TAM have been recently linked to the development and progression of multiple myeloma and leukemia, with a critical role in the homing of malignant cells, drug resistance, immune suppression and angiogenesis. As such, this review will summarize the role of TAM in different hematologic malignancies, focusing on the complex interplay between TAM and tumor cells, the prognostic value of TAM and the possible TAM-targeted therapeutic strategies.

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Section: Tam Role In Leukemiamentioning

confidence: 99%

The Role of Tumor-Associated Macrophages in Hematologic Malignancies

Cencini

Fabbri

Sicuranza

et al. 2021

Cancers

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“…Ventoclax combined with other drugs can increase chemosensitivity, prevent drug resistance, and reduce the incidence of dose-dependent side effects of chemotherapy compared to the single agent use of this drug. Moreover, several clinical cases of ETP-ALL have proven that ventoclax combined with low-intensity chemotherapy ( 158 ), nelarabine ( 159 ), decitabine ( 160 ) or bortezomib ( 161 ) has a good antileukemia effect.…”

Section: Treatment Strategiesmentioning

confidence: 99%

Novel Treatments for Pediatric Relapsed or Refractory Acute B-Cell Lineage Lymphoblastic Leukemia: Precision Medicine Era

2022

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With the markedly increased cure rate for children with newly diagnosed pediatric B-cell acute lymphoblastic leukemia (B-ALL), relapse and refractory B-ALL (R/R B-ALL) remain the primary cause of death worldwide due to the limitations of multidrug chemotherapy. As we now have a more profound understanding of R/R ALL, including the mechanism of recurrence and drug resistance, prognostic indicators, genotypic changes and so on, we can use newly emerging technologies to identify operational molecular targets and find sensitive drugs for individualized treatment. In addition, more promising and innovative immunotherapies and molecular targeted drugs that are expected to kill leukemic cells more effectively while maintaining low toxicity to achieve minimal residual disease (MRD) negativity and better bridge hematopoietic stem cell transplantation (HSCT) have also been widely developed. To date, the prognosis of pediatric patients with R/R B-ALL has been enhanced markedly thanks to the development of novel drugs. This article reviews the new advancements of several promising strategies for pediatric R/R B-ALL.

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“…Venetoclax is a small molecule, BCL-2-selective BH3 mimetic that spares platelets [ 49 , 51 , 52 ]. The Food and Drug Administration (FDA) approved venetoclax for the treatment of chronic lymphocytic leukemia (CLL) and newly diagnosed AML in adults >75 years in combination with other drugs [ 49 , 53 ]. Venetoclax offers promising potential therapeutic benefits and antileukemic activity, although the possibility of resistance may limit the use of this drug as a single agent [ 54 , 55 ].…”

Section: Novel Approach In T-all Treatmentmentioning

confidence: 99%

“…The combination of ABT-199 and chemotherapeutic agents or other targeted therapies could increase the chemosensitivity of leukemic cells, protect against resistance, and decrease dose-dependent chemotherapeutic side effects [ 51 ]. Venetoclax has shown notable clinical activity in patients with T-ALL in combination with chemotherapy [ 53 , 56 ], decitabine [ 53 ], nelarabine [ 57 ], and bortezonib (VEBO) [ 55 ], especially for patients with R/R T-ALL. A phase I study ( identifier: NCT03236857) to evaluate the safety and pharmacokinetics of venetoclax and to determine the dose-limiting toxicity is recruiting pediatric and young adult patients with relapsed or refractory ALL.…”

Section: Novel Approach In T-all Treatmentmentioning

confidence: 99%

The New Therapeutic Strategies in Pediatric T-Cell Acute Lymphoblastic Leukemia

Lato

Przysucha

Grosman

et al. 2021

IJMS

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Childhood acute lymphoblastic leukemia is a genetically heterogeneous cancer that accounts for 10–15% of T-cell acute lymphoblastic leukemia (T-ALL) cases. The T-ALL event-free survival rate (EFS) is 85%. The evaluation of structural and numerical chromosomal changes is important for a comprehensive biological characterization of T-ALL, but there are currently no genetic prognostic markers. Despite chemotherapy regimens, steroids, and allogeneic transplantation, relapse is the main problem in children with T-ALL. Due to the development of high-throughput molecular methods, the ability to define subgroups of T-ALL has significantly improved in the last few years. The profiling of the gene expression of T-ALL has led to the identification of T-ALL subgroups, and it is important in determining prognostic factors and choosing an appropriate treatment. Novel therapies targeting molecular aberrations offer promise in achieving better first remission with the hope of preventing relapse. The employment of precisely targeted therapeutic approaches is expected to improve the cure of the disease and quality of life of patients. These include therapies that inhibit Notch1 activation (bortezomib), JAK inhibitors in ETP-ALL (ruxolitinib), BCL inhibitors (venetoclax), and anti-CD38 therapy (daratumumab). Chimeric antigen receptor T-cell therapy (CAR-T) is under investigation, but it requires further development and trials. Nelarabine-based regimens remain the standard for treating the relapse of T-ALL.

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Venetoclax in association with decitabine as effective bridge to transplant in a case of relapsed early T‐cell lymphoblastic leukemia

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 18 publications

References 14 publications

The Role of Tumor-Associated Macrophages in Hematologic Malignancies

The Role of Tumor-Associated Macrophages in Hematologic Malignancies

Novel Treatments for Pediatric Relapsed or Refractory Acute B-Cell Lineage Lymphoblastic Leukemia: Precision Medicine Era

The New Therapeutic Strategies in Pediatric T-Cell Acute Lymphoblastic Leukemia

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