CLL

Acalabrutinib in treatment-naive chronic lymphocytic leukemia

Acalabrutinib in treatment-naive chronic lymphocytic leukemia

Acalabrutinib, is a second generation BTK inhibitor, which has shown efficacy in relapsed/refractory chronic lymphocytic leukemia.  Monotherapy with acalabrutinib, in treatment naïve CLL patients, in a single-arm phase 1/2 trial were evaluated and reported here.  Eligible adults had either declined or were not eligible for chemotherapy.  The median age was 64. 47% of patients had Rai stage III or IV disease.  Acalabrutinib was administered orally 200 mg once daily or 100 mg twice daily until progression or intolerance.  99 patients were treated.  62% had unmutated immunoglobulin heavy chain variable gene.  18% at T p53 aberrations.  After meeting follow-up with 53 months, 85 patients remained on treatment.  14 discontinued treatment mostly because of adverse events.  The overall response rate was 97%, 90% partial response, 7% complete response.  The outcomes were similar in all prognostic subgroup.  Twice daily dosing revealed improved trough BTK receptor occupancy.  

The median duration of response was not reached, 48-month duration of response rate was 97%.  Serious adverse events were reported and 38 patients.  Adverse events required discontinuation in 6 patients, because of a second primary cancer, n=4 an infection, n=2.  Grade 3 and 4 events of special interest included infection, 15%, hypertension, 11%, bleeding events, 3%, atrial fibrillation, 2%.  The authors concluded “durable efficacy and long-term safety of a acalabrutinib in this trial supports using clinical management of symptomatic, untreated patients with CLL.”

https://ashpublications.org/blood/article-abstract/137/24/3327/475651/Acalabrutinib-in-treatment-naive-chronic?redirectedFrom=fulltext

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