Pretreatment with ibrutinib reduces cytokine secretion and limits the risk of obinutuzumab-induced infusion-related reactions in patients with CLL: analysis from the iLLUMINATE study

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F21%3A10432348" target="_blank" >RIV/00216208:11150/21:10432348 - isvavai.cz</a>

Alternative codes found

RIV/00179906:_____/21:10432348

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=kUup5H3CDy" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=kUup5H3CDy</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00277-021-04536-6" target="_blank" >10.1007/s00277-021-04536-6</a>

Result language

angličtina

Original language name

Pretreatment with ibrutinib reduces cytokine secretion and limits the risk of obinutuzumab-induced infusion-related reactions in patients with CLL: analysis from the iLLUMINATE study

Original language description

Anti-CD20 antibody treatments, such as obinutuzumab, have been associated with infusion-related reactions (IRRs). In the phase 3 iLLUMINATE study of ibrutinib-obinutuzumab versus chlorambucil-obinutuzumab in first-line chronic lymphocytic leukemia/small lymphocytic lymphoma, IRRs were substantially reduced with ibrutinib-obinutuzumab versus chlorambucil-obinutuzumab. We prospectively analyzed inflammatory cytokines to evaluate the impact of ibrutinib on circulating cytokine levels following obinutuzumab infusion. In iLLUMINATE, ibrutinib or chlorambucil was given approximately 30-120 min before the first obinutuzumab infusion. Cytokines evaluated were IFN gamma, IL-6, IL-8, IL-10, IL-18, MCP-1, MIP-1 alpha, MIP-1 beta, and TNF alpha. Changes in peak cytokine levels from baseline (immediately before obinutuzumab) to post-obinutuzumab infusion were compared between arms and between patients with versus without IRRs using Wilcoxon rank sum test. Of 228 treated patients, 95 on ibrutinib-obinutuzumab (15 with IRRs, 80 without) and 88 on chlorambucil-obinutuzumab (45 with IRRs, 43 without) with cytokine data were included. Irrespective of IRR occurrence, median increase in cytokines was lower with ibrutinib-obinutuzumab versus chlorambucil-obinutuzumab for all cytokines (P &lt; 0.01) except MIP-1 beta. Across treatment arms, post-obinutuzumab median increase in all cytokines except MIP-1 beta was greater in patients with versus without IRRs (P &lt; 0.001). IL-6 and IL-8 elevations were associated with IRRs in both treatment arms. Among patients with IRRs, those receiving ibrutinib-obinutuzumab had lower post-obinutuzumab increases in IL-6, IL-8, IL-10, and MCP-1 (P &lt; 0.04) than patients receiving chlorambucil-obinutuzumab. For patients in the ibrutinib-treatment arm, we observed a reduction in both the rate of clinically apparent IRRs and the levels of IRR-related cytokines and chemokines. This observation supports an immunomodulatory mechanism of action for ibrutinib. Clinical Trial Registration: NCT02264574

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30205 - Hematology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Annals of Hematology

ISSN

0939-5555

e-ISSN

—

Volume of the periodical

100

Issue of the periodical within the volume

7

Country of publishing house

DE - GERMANY

Number of pages

10

Pages from-to

1733-1742

UT code for WoS article

000652431500001

EID of the result in the Scopus database

2-s2.0-85106243319