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Ibrutinib inhibits antibody dependent cellular cytotoxicity induced by rituximab or obinutuzumab in MCL cell lines, not overcome by addition of lenalidomide

Albertsson-Lindblad, Alexandra LU ; Freiburghaus, Catja LU ; Jerkeman, Mats LU and Ek, Sara LU (2019) In Experimental Hematology and Oncology 8(1).
Abstract

Background: The Bruton's Tyrosine Kinase (BTK)-inhibitor ibrutinib is highly active in mantle cell lymphoma (MCL) but may inhibit response to anti-CD20 antibody as previously shown in CLL models. We investigated how antibody-dependent cellular cytotoxicity (ADCC) induced by type I/II anti-CD20 antibodies was affected by treatment with ibrutinib in MCL. Furthermore, we investigated if lenalidomide, a potential sensitizer to anti-CD20 treatment, could prevent an inhibitory effect of ibrutinib. Methods: Anti-CD20 (rituximab/obinutuzumab) opsonized MCL cell lines were co-cultured with ibrutinib (± lenalidomide) - exposed effector cells, and analyzed for evaluation of cell death. Results: Cell death induced by rituximab was reduced with 75%... (More)

Background: The Bruton's Tyrosine Kinase (BTK)-inhibitor ibrutinib is highly active in mantle cell lymphoma (MCL) but may inhibit response to anti-CD20 antibody as previously shown in CLL models. We investigated how antibody-dependent cellular cytotoxicity (ADCC) induced by type I/II anti-CD20 antibodies was affected by treatment with ibrutinib in MCL. Furthermore, we investigated if lenalidomide, a potential sensitizer to anti-CD20 treatment, could prevent an inhibitory effect of ibrutinib. Methods: Anti-CD20 (rituximab/obinutuzumab) opsonized MCL cell lines were co-cultured with ibrutinib (± lenalidomide) - exposed effector cells, and analyzed for evaluation of cell death. Results: Cell death induced by rituximab was reduced with 75% at 0.5 μM ibrutinib and with 52% at 0.1 μM ibrutinib when induced by obinutuzumab, even by addition of lenalidomide. Moreover, obinutuzumab was associated with higher rate of cell death compared to rituximab. Conclusion: Ibrutinib negatively affects anti-CD20 induced cell death in MCL, not reversed by lenalidomide. Explorations of sequential administration and selective BTK-inhibitors may reveal the optimal combination of novel agents in MCL.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antibody-dependent cell death, CD20 antibody, Ibrutinib, Lenalidomide, Mantle cell lymphoma
in
Experimental Hematology and Oncology
volume
8
issue
1
article number
16
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85070479304
  • pmid:31406628
ISSN
2162-3619
DOI
10.1186/s40164-019-0141-1
language
English
LU publication?
yes
id
9af8f3c4-2fd6-4431-b38b-faf1b632013b
date added to LUP
2019-08-30 14:00:13
date last changed
2021-04-06 02:57:37
@article{9af8f3c4-2fd6-4431-b38b-faf1b632013b,
  abstract     = {<p>Background: The Bruton's Tyrosine Kinase (BTK)-inhibitor ibrutinib is highly active in mantle cell lymphoma (MCL) but may inhibit response to anti-CD20 antibody as previously shown in CLL models. We investigated how antibody-dependent cellular cytotoxicity (ADCC) induced by type I/II anti-CD20 antibodies was affected by treatment with ibrutinib in MCL. Furthermore, we investigated if lenalidomide, a potential sensitizer to anti-CD20 treatment, could prevent an inhibitory effect of ibrutinib. Methods: Anti-CD20 (rituximab/obinutuzumab) opsonized MCL cell lines were co-cultured with ibrutinib (± lenalidomide) - exposed effector cells, and analyzed for evaluation of cell death. Results: Cell death induced by rituximab was reduced with 75% at 0.5 μM ibrutinib and with 52% at 0.1 μM ibrutinib when induced by obinutuzumab, even by addition of lenalidomide. Moreover, obinutuzumab was associated with higher rate of cell death compared to rituximab. Conclusion: Ibrutinib negatively affects anti-CD20 induced cell death in MCL, not reversed by lenalidomide. Explorations of sequential administration and selective BTK-inhibitors may reveal the optimal combination of novel agents in MCL.</p>},
  author       = {Albertsson-Lindblad, Alexandra and Freiburghaus, Catja and Jerkeman, Mats and Ek, Sara},
  issn         = {2162-3619},
  language     = {eng},
  month        = {08},
  number       = {1},
  publisher    = {BioMed Central (BMC)},
  series       = {Experimental Hematology and Oncology},
  title        = {Ibrutinib inhibits antibody dependent cellular cytotoxicity induced by rituximab or obinutuzumab in MCL cell lines, not overcome by addition of lenalidomide},
  url          = {http://dx.doi.org/10.1186/s40164-019-0141-1},
  doi          = {10.1186/s40164-019-0141-1},
  volume       = {8},
  year         = {2019},
}