Can Acalabrutinib Raise WBC?
Yes, acalabrutinib causes transient lymphocytosis (elevated white blood cell count) in most patients through early mobilization of lymphocytes from tissue compartments into peripheral blood, and this does not signify disease progression. 1
Mechanism and Clinical Significance
Acalabrutinib, as a Bruton tyrosine kinase inhibitor, causes early mobilization of lymphocytes into the blood, resulting in transient lymphocytosis in most patients. 1
This lymphocytosis represents redistribution of malignant lymphocytes from lymph nodes and spleen into circulation, not proliferation or disease progression. 1
The NCCN guidelines explicitly state that prolonged lymphocytosis after acalabrutinib treatment represents persistence of a quiescent clone, and slow or incomplete resolution does not impact progression-free survival. 1
Revised Response Criteria
The International Workshop on Chronic Lymphocytic Leukemia (IWCLL) created a new response category—"partial response with lymphocytosis"—specifically for patients receiving acalabrutinib or other BTK inhibitors. 1
Isolated progressive lymphocytosis in the setting of reduced lymph node size, reduced organomegaly, or improvement in hemoglobin/platelets will NOT be considered progressive disease. 1
Clinical response is defined by reduction in lymph nodes and splenomegaly with persistent lymphocytosis, in the absence of other indicators of progressive disease. 1
Critical Clinical Pitfall
Do not discontinue acalabrutinib or escalate therapy based solely on rising WBC counts if lymph nodes are shrinking and the patient is otherwise improving clinically. 1
The lymphocytosis typically resolves over time as the malignant clone is suppressed, though complete resolution may take months and is not required for therapeutic benefit. 1
Hematologic Toxicity Profile
Grade ≥3 neutropenia occurs in 14-26% of patients on acalabrutinib monotherapy, and increases to approximately 30% when combined with obinutuzumab. 2
Grade ≥3 lymphocytosis (as a laboratory abnormality) is not typically reported as a toxicity in clinical trials, reinforcing that elevated lymphocyte counts are an expected pharmacodynamic effect rather than an adverse event. 3