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The Role of PI3K Inhibition in Lymphoid Malignancies

  • B-cell NHL, T-cell NHL, and Hodgkin Lymphoma (J Amengual, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The outcome of patients with lymphoid malignancies has markedly improved in recent years which is likely due to a combination of advances in supportive care, and therapeutic options. In this article, we will provide an overview over the role PI3-kinase signalling, one of the most important dysregulated pathways in cancer, and its successful inhibition in lymphoma.

Recent Findings

PI3-kinase inhibitors have shown remarkable activity in an increasing subset of patients with non-Hodgkin lymphomas. The first drug to be approved was idelalisib for patients with relapsed/refractory follicular lymphoma and CLL/SLL as monotherapy, or in combination with rituximab, respectively. After an initial setback related to increased toxicity including deaths observed in several upfront studies, there has been a resurgence in interest in this pathway following the promising efficacy of second-generation PI3K inhibitors including in patients with T cell lymphomas.

Summary

PI3K inhibition continues to be an invaluable tool in the therapy of patients with lymphoid malignancies if managed cautiously. Preclinical models are helpful in predicting possible side effects and identifying new lymphoma subtypes that may be susceptible to this class of agents. The future will likely involve rationally designed combinatorial approaches to deepen the response rate and prevent the emergence of resistance.

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  1. Memorial Sloan Kettering Cancer Center, Lymphoma Service, New York, NY, USA

    Gottfried von Keudell & Alison J. Moskowitz

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  1. Gottfried von Keudell
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Correspondence to Alison J. Moskowitz.

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Conflict of Interest

Gottfried von Keudell has received consulting honoraria from Genentech, Pharmacyclics, and Bayer.

Alison J. Moskowitz has received research support from Seattle Genetics, Merck, Bristol-Myers Squibb, and Incyte. In addition, she has received honorarium from Kyowa Hakko Kirin Pharma, Miragen Therapeutics, Takeda Pharmaceuticals, ADC Therapeutics, Seattle Genetics, Cell Medica, Bristol-Myers Squibb, and Erytech Pharma.

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von Keudell, G., Moskowitz, A.J. The Role of PI3K Inhibition in Lymphoid Malignancies. Curr Hematol Malig Rep 14, 405–413 (2019). https://doi.org/10.1007/s11899-019-00540-w

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