Ibrutinib Efficacy, Safety, and Pharmacokinetics in Chinese Patients with Relapsed or Refractory Waldenström's Macroglobulinemia: A Multicenter, Single-Arm, Phase 4 Study

Introduction: Waldenström's macroglobulinemia (WM) is a rare malignant B cell lymphoma which occurs in around 1-2% of all hematologic tumors. Ibrutinib was approved in China for WM on the basis of two global pivotal studies which enrolled no Chinese patients. The aim of this study was to determine the efficacy, safety, and pharmacokinetics of ibrutinib in Chinese patients with relapsed or refractory (r/r) WM.

Methods: This was an open-label, single-arm, multicenter phase 4 study conducted across five sites in China. Enrolled patients with clinicopathological confirmed WM received ibrutinib 420 mg once daily orally until disease progression or unacceptable toxicity. The primary endpoint was major response rate (MRR, partial response [PR], or better) according to the modified consensus criteria from the Sixth International Workshop on WM.

Results: Seventeen patients were enrolled; at data cutoff (March 19, 2022), MRR was 64.7% (90% confidence interval [CI] 42.0-83.4) and overall response rate was 100% (90% CI 83.8-100.0). One (5.9%) patient achieved very good PR, 10 (58.8%) achieved PR, and six (35.3%) achieved minor response. The median duration of response (PR or better) was 14.8 months (95% CI 10.8-not estimable [NE]). Median progression-free survival was 18.4 months (95% CI 12.9-NE). All patients experienced at least one treatment-emergent adverse event (TEAE) related to the study drug, and grade ≥ 3 TEAEs were reported in 13 (76.5%) patients. There were no TEAEs leading to dose reduction or death. The median model estimated maximum plasma concentration and area under the plasma concentration-time curve during 24 h after dosing at steady state were 40.5 ng/mL and 204 ng·h/mL, respectively.

Conclusions: Ibrutinib demonstrated durable responses in Chinese patients with r/r WM. Treatment was well tolerated with no new safety signals compared with the pivotal global studies. Ibrutinib exposure was also comparable between Chinese and non-Chinese patients.

Trial registration: ClinicalTrials.gov identifier NCT04042376.