Prolonged lymphocytosis during Ibrutinib therapy

The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has outstanding activity in patients with chronic lymphocytic leukemia. Most patients experience lymphocytosis, representing lymphocyte egress from nodal compartments.

This resolves within 8 months in the majority of patients, but a subgroup has lymphocytosis lasting >12 months. Here we report a detailed characterization of patients with persistent lymphocytosis during ibrutinib therapy. Signaling evaluation showed that while BTK is inhibited, downstream mediators of B-cell receptor (BCR) signaling are activated in persistent lymphocytes. These cells cannot be stimulated through the BCR and do not show evidence of target gene activation.

Progression-free survival is not inferior for patients with prolonged lymphocytosis vs those with traditional responses. Thus, prolonged lymphocytosis is common following ibrutinib treatment, likely represents the persistence of a quiescent clone, and does not predict a subgroup of patients likely to relapse early.

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Ibrutinib Approved for treatment of patients with mantle cell lymphoma; Chronic lymphocytic leukemia is not far behind

The FDA approved the use of ibrutinib, now known as Imbruvica, for the treatment of patients with mantle cell lymphoma.  Ibrutinib is the second drug with ‘breakthrough therapy designation’ to receive FDA approval.  This effort is appaluded and supported by the Leukemia and Lymphoma Society (LLS).  We are also proud to mention that the program is lead by former BCRF fellow, Danelle James, MD, MS. (Medical Director for Pharmacyclics)