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Radiation Oncology

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Open Access 01-12-2017 | Research

Idelalisib may have the potential to increase radiotherapy side effects

Authors: Thomas Gryc, Florian Putz, Nicole Goerig, Sonia Ziegler, Rainer Fietkau, Luitpold V. Distel, Barbara Schuster

Published in: Radiation Oncology | Issue 1/2017

Abstract

Introduction

Idelalisib is approved for the treatment of relapsed chronic lymphocytic leukemia together with Rituximab and for monotherapy of follicular B-cell non-Hodgkin’s lymphoma and small lymphocytic lymphoma. It is a potent and selective phosphatidylinositol 3-kinase-δ (PI3K-δ) inhibitor. PI3K-δ primarily is expressed in B-cells and prevents effectively proliferation in malignant B-cells.

Methods

We provide a detailed report on treatment history and photo documentation of acute adverse effects of radiation therapy with simultaneous Idelalisib medication in one case of B-CLL. Radiosensitivity tests were performed for the index patient under Idelalisib and after the addition of Idelalisib to healthy individuals’ blood. Radiosensitivity in human lymphocytes was analyzed with a three color in situ hybridization assay. Primary skin fibroblasts were studied after a treatment with Idelalisib for apoptosis, necrosis and cell cycle using flow cytometry. DNA double-strand break repair was analyzed by γH2AX immunostaining.

Results

The index patient presented a strong grade 2 radiodermatitis and grade 3 mucositis after irradiation with 20 Gy and a simultaneous intake of Idelalisib. Irradiations without Idelalisib medication were well tolerated and resulted in not more than grade 1 radiodermatitis. The index patient under Idelalisib had a radiosensitivity of 0.62 B/M which is in the range of clearly radiosensitive patients. A combined treatment of lymphocytes with 2 Gy and 10 nmol/l Idelalisib showed a tendency to an increased radiosensitivity. We found a clear increase of apoptosis as a result of the combined treatment in the Idelalisib dose range of 1 to 100 nmol/l compared to solely irradiated cells or solely Idelalisib treated cells (p = 0.05).

Conclusion

A combined Idelalisib radiotherapy treatment has an increased risk of side effects. However, combined therapy seems to be feasible when patients are monitored closely.

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Title: Idelalisib may have the potential to increase radiotherapy side effects
Authors: Thomas Gryc
Florian Putz
Nicole Goerig
Sonia Ziegler
Rainer Fietkau
Luitpold V. Distel
Barbara Schuster
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Radiation Oncology / Issue 1/2017
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/s13014-017-0827-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Idelalisib may have the potential to increase radiotherapy side effects

Abstract

Introduction

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

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