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- Albertsson-Lindblad, Alexandra, et al.
(author)
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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
- 2019
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In: Experimental Hematology and Oncology. - : Springer Science and Business Media LLC. - 2162-3619. ; 8:1
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Journal article (peer-reviewed)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% 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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| 2. |
- Albertsson-Lindblad, Alexandra, et al.
(author)
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Is there a role for immunomodulatory drugs in the treatment of mantle cell lymphoma?
- 2019
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In: Annals of Lymphoma. - 2616-2695. ; 3:2, s. 1-15
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Journal article (peer-reviewed)abstract
- Although survival has improved in patients with mantle cell lymphoma (MCL) during the last two decades, thanks to intensified approach upfront and with anti-CD20 targeted treatment, the disease is still regarded as incurable and for the elderly/unfit patient population, there is need for more tolerable and effective treatment options. Immunomodulatory drugs (IMiDs) have demonstrated activity in MCL and could be regarded as attractive components of combinatory regimens for MCL, in light of their broad spectrum of activity and the potency to synergize with monoclonal antibody treatment. This review focus on the role of lenalidomide (L) as single agent in R/R MCL and in combinatory regimens. To date, one can conclude that L is an active agent in MCL, preferably when combined with anti-CD20 antibody, and may have a role as upfront treatment of elderly/unfit patients. Moreover, regimens including lenalidomide in combination with immunochemotherapy and in chemo-free regimens have shown activity, albeit associated with an increased risk of dose-limiting toxicity in untreated patient populations. Randomized trials evaluating the addition of L upfront, and phase I/II trials on L combined with other novel agents such as BTK- and bcl-2 inhibitors are underway and will further bring insight into the role of IMiDs in MCL.
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