Acalabrutinib Monotherapy May Be Effective in the Treatment of Waldenstrom Macroglobulinemia
Previous studies have shown that acalabrutinib monotherapy may lead to improved outcomes among patients with treatment-naive or relapsed/refractory Waldenstrom macroglobulinemia.
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CHICAGO—Acalabrutinib is a durable and well-tolerated effective therapeutic option for patients with Waldenstrom macroglobulinemia (WM), according findings presented at the American Society of Clinical Oncology 2018 Annual Meeting on Sunday, June 3.1
The inhibition of Bruton tyrosine kinase (BTK) is an effective treatment strategy in WM; ibrutinib has been approved for treatment of WM but is associated with toxicities such as bleeding and atrial fibrillation. Previous studies have shown that acalabrutinib monotherapy — a highly selective BTK inhibitor — may lead to improved outcomes among patients with treatment-naive (TN) or relapsed/refractory (R/R) WM.
For this phase 2 study (ClinicalTrials.gov Identifier: NCT02180724), researchers assigned 106 patients with WM to receive oral acalabrutinib 100 mg twice daily or 200 mg once daily until disease progression or intolerable toxicity occurred. Patients who had failed previous therapies (92 patients) or were never treated (14 patients) were eligible for the study. Previous BTK inhibitor therapy was an exclusion criteria.
After a median 27.4 months of follow-up, the overall response rate (ORR) was 93% among both TN and R/R patients, and the major response rate was 79% and 80%, respectively.
A subgroup analysis of patients who were treated with at least 3 lines of previous therapy showed the ORR was 95.5%, and was 93.4% among patients who were aged at least 65 years.
The median duration of response (DOR) was not yet evaluable at the time of analysis, but 2-year rates of DOR, progression-free survival (PFS), and overall survival (OS) were 90%, 90%, and 91.7% among patients with treatment-naive WM, respectively, and among patients with R/R WM these rates were 82%, 81.9%, and 88.9%, respectively.
Fifty percent (7) of treatment-naive patients and 76% (70) of relapsed/refractory patients were still on acalabrutinib therapy at the time of analysis; 9 patients discontinued treatment due to disease progression, 3 patients in the treatment-naive and 6 patients in R/R groups had intolerable adverse effects (AE).
The most frequently reported AEs included headache, diarrhea, contusion, dizziness, and the most common grade 3 to 4 AEs were neutropenia, pneumonia, anemia, increased ALT, and hyponatremia. Fifty-six percent of patients experienced a bleeding AE, and grade 5 AEs included pneumonia, glioblastoma multiforme, esophageal carcinoma, myocardial ischemia, and intracranial hematoma.
BTK occupancy and pharmacokinetic parameters were consistent with previously reported data.
The authors concluded that “these results indicate that acalabrutinib has substantial activity and favorable tolerability in patients with WM.”
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- Owen R, McCarthy H, Rule S, et al. Acalabrutinib in patients (pts) with Waldenström macroglobulinemia (WM). Oral presentation at: 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL.