Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages.

BORGE MERCEDES; ALMEJÚN MARÍA BELÉN; PODAZA ENRIQUE; COLADO ANA; CABREJO MARÍA; FERNANDEZ GRECCO HORACIO; BEZARES FERNANDO RAIMUNDO; GIORDANO MIRTA; GAMBERALE ROMINA

HAEMATOLOGICA

FERRATA STORTI FOUNDATION

Año: 2015

0390-6078

Chronic lymphocytic leukemia (CLL) is the most common leukemia of adults and is still an incurable disease. Current therapies are effective in inducing initial remission in most patients but they are not curative and relapse is inevitable (1). Moreover, the most effective chemoimmunotherapy regimens like fludarabine, cyclophosphamide and rituximab are not well tolerated by many older patients and infection complications are not rare (2, 3). Treatment of CLL patients with Ibrutinib, an oral irreversible inhibitor of the Bruton Tyrosine Kinase, has shown promising efficacy and excellent tolerability. The combination of Ibrutinib with different targeted therapies is now being explored. In a single arm study, the combination of Ibrutinib and rituximab in patients with high-risk CLL was generally well-tolerated and resulted in an OR rate of 95% and a PFS of 78% at 18-months (4), the added effect of rituximab to the Ibrutinb therapy is being test in a randomized trial testing Ibrutinb versus Ibrutinb and rituximab (NCT02007044). Given that macrophages are the most important effector cells in the anti-CD20-therapeutic effect in murine models (5, 6) and they probably play a key role in human anti-CD20 therapy (7, 8), we ask whether Ibrutinib could interfere with the capacity of human macrophages to mediate phagocytosis of rituximab-coated CLL cells. Our results showed that Ibrutinib impairs the phagocytosis of rituximab-opsonized CLL cells by human macrophages.