Orelabrutinib Monotherapy May Be an Option for Relapsed/Refractory Waldenström’s Macroglobulinemia

Orelabrutinib—a novel, small molecule, selective irreversible Bruton’s tyrosine kinase inhibitor—demonstrated promising safety and efficacy in patients with relapsed/refractory Waldenström’s macroglobulinemia (WM), according to a trial in China.

The prospective, multicenter trial enrolled 66 patients with WM who received at least one prior line of therapy between August 2019 and December 2020 at 15 hospitals in China. Median patient age was 63 years (range, 47-80 years), and 85.1% of patients were male. Patients received orelabrutinib 150 mg orally daily until disease progression or unacceptable toxicity.

After a median follow-up of 16.4 months (range, 12.5-19.5 months), 47 patients were eligible for efficacy assessment. The major response rate (MRR; primary endpoint) was 80.9%, and the overall response rate was 89.4% with orelabrutinib. Median time to at least a minor response was 1.9 months. The 12-month progression-free survival rate was 89.4%.

Among patients with MYD88L265P/CXCR4NEG, MYD88L265P/CXCR4^S338X, and MYD88NEG/CXCR4NEG mutations, MRR was 84.6%, 100%, and 25%, respectively.

A majority (91%) of adverse events were grade 1/2. The most common grade ≥3 adverse events were neutropenia (10.6%), thrombocytopenia (6.4%), and pneumonia (4.3%). Ten patients (21.3%) reported serious adverse events, and one treatment-related death was reported in a patient with hepatitis B reactivation.

“In summary, orelabrutinib monotherapy in relapsed/refractory WM patients showed a deep and durable response with favorable safety, resulting from high target selectivity,” the authors concluded. “These study results indicate that orelabrutinib has the potential to be a suitable therapeutic choice for patients with relapsed/refractory WM.”

Reference

Cao X, Jin J, Fu C, et al. Evaluation of orelabrutinib monotherapy in patients with relapsed or refractory Waldenström’s macroglobulinemia in a single-arm, multicenter, open-label, phase 2 study. eClinical Medicine. 2022. doi:10.1016/j.eclinm.2022.101682