In Human Visualization of Ibrutinib-Induced CLL Compartment Shift

Area of Science:

• Oncology
• Hematology
• Medical Imaging

Background:

• Ibrutinib is an effective Bruton tyrosine kinase inhibitor for chronic lymphocytic leukemia (CLL).
• Patients often experience increased CLL blood cell counts after initiating ibrutinib, hypothesized to be a "compartment shift" from lymph nodes to blood.
• The precise mechanism and in vivo demonstration of this CLL cell redistribution remain unclear.

Purpose of the Study:

• To visualize and demonstrate the topical changes and "compartment shift" of CLL cells in vivo during ibrutinib treatment.
• To investigate the role of CXCR4 expression in CLL cell redistribution.
• To refine the mechanistic model of ibrutinib's effect on CLL cell localization.

Main Methods:

• Utilized [⁶⁸Ga]Pentixafor-PET/MRI for in vivo visualization of CXCR4 expression in CLL patients.
• Monitored changes in radiotracer uptake in bone marrow, lymph nodes, and spleen within the first month of ibrutinib treatment.
• Correlated imaging findings with changes in blood cell counts (leukocytosis) and tissue volumes.

Main Results:

• Early ibrutinib treatment showed decreased [⁶⁸Ga]Pentixafor uptake in bone marrow and lymph nodes, with increased uptake in the spleen.
• Leukocytosis and the number of CXCR4^high CLL cells increased, while lymph node and spleen volumes decreased.
• Prolonged treatment led to decreased leukocytosis and splenic [⁶⁸Ga]Pentixafor uptake, suggesting CLL cell redistribution.

Conclusions:

• The study provides in vivo imaging evidence supporting the "compartment shift" hypothesis of CLL cells from lymph nodes to peripheral blood.
• Early bone marrow clearing and redistribution to the spleen are key early mechanisms.
• Findings refine the understanding of ibrutinib's impact on CLL cell trafficking and localization.