Venetoclax treatment of patients with relapsed T-cell prolymphocytic leukemia

Hampel, Paul J.; Call, Timothy G.; Shah, Mithun Vinod; Bennani, N. Nora; Al‐Kali, Aref; Rabe, Kari G.; Wang, Yucai; Muchtar, Eli; Leis, José F.; Kenderian, Saad S.; Koehler, Amber B.; Schwager, Susan M.; Slager, Susan L.; Kay, Neil E.; Hanson, Curtis A.; Dyke, Daniel L. Van; Shi, Min; Ding, Wei

doi:10.1038/s41408-021-00443-1

Cited by 8 publications

(11 citation statements)

References 17 publications

(27 reference statements)

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“…10,16 First encouraging clinical data derive from combinations of venetoclax with bendamustine, with pentostatin, with ibrutinib (see also phase II trial NCT03873493), or with MCL1 inhibitors. 15,[17][18][19] In T-LGL, alterations of the BCL2/MCL1 equilibrium have been reported as well and were linked to overactivated STAT3. To our knowledge, there is no published data on the efficacy of therapeutic BCL2-family modulation in T-LGL.…”

Section: P53 Reactivation and Targeting Of The Bcl2 Familymentioning

confidence: 96%

“…8 However, several small case series indicate that in r/r T-PLL venetoclax as a single agent does not impose good tumor control; for example, median OS of 32.5 days from start of treatment. 15 Synergistic effects of venetoclax with inhibitors of ITK, JAK/STAT, or HDAC, are reported from preclinical tests. 10,16 First encouraging clinical data derive from combinations of venetoclax with bendamustine, with pentostatin, with ibrutinib (see also phase II trial NCT03873493), or with MCL1 inhibitors.…”

Section: P53 Reactivation and Targeting Of The Bcl2 Familymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Synergistic effects of venetoclax with inhibitors of ITK, JAK/STAT, or HDAC, are reported from preclinical tests 10,16 . First encouraging clinical data derive from combinations of venetoclax with bendamustine, with pentostatin, with ibrutinib (see also phase II trial NCT03873493), or with MCL1 inhibitors 15,17–19 …”

Section: Introductionmentioning

confidence: 99%

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Hijacking the Pathway: Perspectives in the Treatment of Mature T-cell Leukemias

Wahnschaffe

Herling

2021

HemaSphere

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Section: P53 Reactivation and Targeting Of The Bcl2 Familymentioning

confidence: 96%

Section: P53 Reactivation and Targeting Of The Bcl2 Familymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hijacking the Pathway: Perspectives in the Treatment of Mature T-cell Leukemias

Wahnschaffe

Herling

2021

HemaSphere

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“…Venetoclax) (10,59,60). There are ongoing activities in the search for efficacious combinations of the, as single agent clinically only moderately active Venetoclax, with other classes of inhibitors in relapsed/ refractory (r/r) T-PLL (59)(60)(61)(62). In addition, epigenetic disturbances of T-PLL cells further emphasize hypomethylating agents (e.g.…”

Section: Clinical Implications Derived From the Current Disease Modelmentioning

confidence: 99%

Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact

et al. 2021

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T-cell prolymphocytic leukemia (T-PLL) is the most common mature T-cell leukemia. It is a typically aggressively growing and chemotherapy-resistant malignancy with a poor prognosis. T-PLL cells resemble activated, post-thymic T-lymphocytes with memory-type effector functions. Constitutive transcriptional activation of genes of the T-cell leukemia 1 (TCL1) family based on genomic inversions/translocations is recognized as a key event in T-PLL’s pathogenesis. TCL1’s multiple effector pathways include the enhancement of T-cell receptor (TCR) signals. New molecular dependencies around responses to DNA damage, including repair and apoptosis regulation, as well as alterations of cytokine and non-TCR activation signaling were identified as perturbed hallmark pathways within the past years. We currently witness these vulnerabilities to be interrogated in first pre-clinical concepts and initial clinical testing in relapsed/refractory T-PLL patients. We summarize here the current knowledge on the molecular understanding of T-PLL’s pathobiology and critically assess the true translational progress around this to help appraisal by caregivers and patients. Overall, the contemporary concepts on T-PLL’s pathobiology are condensed in a comprehensive mechanistic disease model and promising interventional strategies derived from it are highlighted.

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Prolymphocytic Leukemia

El‐Sharkawiand,

Dearden

2023

Cancer Consult

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Venetoclax treatment of patients with relapsed T-cell prolymphocytic leukemia

Cited by 8 publications

References 17 publications

Hijacking the Pathway: Perspectives in the Treatment of Mature T-cell Leukemias

Hijacking the Pathway: Perspectives in the Treatment of Mature T-cell Leukemias

Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact

Prolymphocytic Leukemia

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