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Acalabrutinib in ibrutinib-intolerant R/R CLL patients
Safety
The most frequent adverse events of any grade occur- ring with acalabrutinib were diarrhea (n=32, 53%), headache (n=25, 42%), contusion (n=24, 40%), dizziness (n=20, 33%), upper respiratory tract infection (n=20, 33%), and cough (n=18, 30%) (Table 2 and Online Supplementary Table S3). The most frequent grade ≥3 adverse events were pneumonia (n=9, 15%), neutropenia (n=7, 12%), increased lymphocyte count (including lym- phocytosis and lymphocyte count increased; n=8, 13%), and thrombocytopenia (including platelet count decreased and thrombocytopenia; n=5, 8%) (Table 2). Serious adverse events of any grade were experienced by 31 (52%) patients. Treatment-related severe adverse events of any grade that were deemed related to acalabru- tinib by the investigator were experienced by ten (17%) patients. There were five dose reductions in four patients; one patient had two dose reductions due to vaginal yeast infection. All four patients had successful adverse event management with dose reduction and continued on study. However, one of these patients later discontinued acalabrutinib due to adverse events.
Ten (16.7%) patients had an adverse event leading to
acalabrutinib discontinuation, including pneumonia (n=2, 1 grade 3 event and 1 death), diarrhea (n=1, grade 2), headache (n=1, grade 1), endometrial cancer (n=1, grade 3), stomatitis (n=1, grade 2), subdural hematoma (n=1, grade 2), cerebrovascular accident (n=1, grade 2), increased transaminases (n=1, grade 4), and squamous cell carcinoma of lung (n=1, grade 2). Among these events, the investigator considered diarrhea, headache, stomatitis, and subdural hematoma to be related to the acalabrutinib treatment. Only one patient discontinued acalabrutinib due to the same adverse event (diarrhea) that resulted in prior ibrutinib discontinuation; grade 3 or 4 diarrhea led to ibrutinib discontinuation and grade 2 diarrhea led to acalabrutinib discontinuation.
To better understand acalabrutinib tolerability follow- ing ibrutinib discontinuation, the incidence of ibrutinib- intolerance adverse events was examined during acal- abrutinib treatment. Among 60 enrolled patients, 27 ibru- tinib-intolerance adverse events occurred in 24 (40%) patients during acalabrutinib treatment. Of these, most events (67% [n=18/27 events in 18 patients) were lower grade on acalabrutinib than on prior ibrutinib treatment; 30% (n=8/27 events in 6 patients) were of an unchanged
Figure 1. Trial profile. AE: adverse events.
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