Does Ibrutinib Pretreatment Reduce the Risk of Obinutuzumab-Related Infusion Reactions in CLL?
Posted: Monday, August 2, 2021
Findings from an analysis of the phase III iLLUMINATE study, presented in the Annals of Hematology, indicate that pretreatment with ibrutinib may be able to reduce infusion-related reactions associated with obinutuzumab treatment for some patients with chronic lymphocytic leukemia (CLL). This result may be related to ibrutinib’ s suppression of the release of inflammatory cytokines and chemokines often induced by obinutuzumab.
“These observations may have implications for immunotherapeutic approaches, where the tuning of the inflammatory reaction may modify the type and degree of cytokine-release patterns (activated or dampened) and their role in the treatment effect or safety profile of immunotherapies,” concluded Fatih Demirkan, MD, of Dokuz Eylül University, Turkey, and colleagues.
The study enrolled 228 patients with treatment-naive CLL who were randomly assigned to receive a combination treatment of either ibrutinib/obinutuzumab (n = 113) or chlorambucil/obinutuzumab (n = 115). Patients experiencing cytokine or chemokine activity (n = 95, ibrutinib arm; n = 88, chlorambucil arm) were included for cytokine/chemokine analysis.
Of those patients, 15 (16%) receiving ibrutinib and 45 (51%) receiving chlorambucil experienced infusion-related reactions on the first day of treatment. In comparison, 80 patients (84%) in the ibrutinib group and 43 patients (49%) in the chlorambucil group experienced no such reactions. The median cytokine increase was lower in the ibrutinib group (P < .01).
Except for MIP-1β, cytokine increases were higher in patients of either group who experienced infusion-related reactions than for those who did not (P < .001). An association between elevated interleukin-6 (IL-6) and IL-8 and infusion-related reactions was observed across treatment arms. Patients in the ibrutinib group who experienced infusion-related reactions had less of an increase in IL-6, IL-8, IL-10, and MCP-1 following obinutuzumab treatment (P < .04).
Disclosure: For full disclosures of the study authors, visit link.springer.com.
