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Does Ibrutinib Therapy Induce Host Antitumor Immune Activation in CLL?

By: Julia Fiederlein
Posted: Monday, May 10, 2021

Targeting the interleukin 2 (IL-2)–inducible kinase with ibrutinib may revert the T helper (Th) 2 polarization observed in patients with chronic lymphocytic leukemia (CLL), according to Robin Foà, MD, of Sapienza University, Rome, and colleagues. The results of the front-line GIMEMA LLC1114 trial were published in Frontiers in Oncology.

“The significant homology between Bruton tyrosine kinase and IL-2–inducible kinase supports the role of ibrutinib as an immunomodulatory inhibitor of both Bruton tyrosine kinase and IL-2–inducible kinase,” the investigators commented. “The association between the Th2/Th1 ratio decrease and the complete response achievement suggests the in vivo generation of a potential host antitumor immune activation induced by ibrutinib.”

A total of 208 peripheral blood samples were collected from 71 patients treated with ibrutinib plus rituximab, followed by maintenance with ibrutinib. According to the investigators, the circulating Th2 cell count seemed to significantly diminish at 8 (P = .019) and 12 (P = .002) months; a significant decrease in the absolute number of Th17 cells was also observed at 8 months (P = .003) and maintained up to 18 months (12 months: P = .003; 18 months: P = .004) of therapy. On the other hand, the investigators reported a relative increase in the absolute Th1 cell count.

The Th2/Th1 ratio seemed to significantly decrease after 14 days of treatment (P = .037); this was maintained after 8 (P = .001), 12 (P = .005), and 18 (P = .002) months. The Th2/Th1 modulation over time seemed to be significant only among patients with unmutated IGHV genes (P < .0001). At 8 months, the Th2/Th1 ratio below a cutoff of 0.088 seemed to be associated with the achievement of a complete response (P = .016).

Disclosure: The study authors reported no conflicts of interest.



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