Venetoclax Safe, Effective in Previously Treated Patients With Waldenström Macroglobulinemia

Venetoclax is safe and effective in previously treated patients with Waldenstrom macroglobulinemia (WM), including those previously exposed to Bruton tyrosine kinase (BTK) inhibitors, according to results from a phase 2 trial.

The trial enrolled 32 patients from the Dana-Farber Cancer Institute, Weill Cornell Medical Center, The City of Hope National Medical Center, and Stanford University Medical Center between June 2016 and February 2018. The date of data cutoff was December 31, 2020. Eligible patients had a diagnosis of WM, received prior treatment, had an Eastern Cooperative Oncology Group performance of ≤ 2, adequate bone marrow function, creatinine clearance ≥ 50 mL/min, and adequate hepatic function.

Relapsed disease was defined as attaining a response to previous therapy and meeting criteria for disease progression beyond 6 months after completing such therapy, while refractory disease was defined as either not attaining a minor response or progressing within 6 months of completing the previous therapy. All of the patients were MYD88 L265P–mutated, 17 carried CXCR4 mutations, and 16 had previously been exposed to BTK inhibitors.

For the first 6 patients, the study drug was administered orally once daily at 200 mg for 1 week, followed by 400 mg for 1 week, and then 800 mg for 2 years. Starting with the seventh patient, venetoclax was administered orally once daily at 400 mg for 1 week, followed by 800 mg for 2 years.

The median follow-up was 33 months. The median time from the previous therapy to venetoclax initiation was 9 months; only 7 patients were treated in the first relapse. Of the 11 refractory participants, 4 were refractory to proteasome inhibitor–based regimens, 3 to BTK inhibitors, 2 to single agent anti-CD20 monoclonal antibodies, 1 to bendamustine and rituximab, and 1 to a phosphatidylinositol-3 kinase inhibitor.

The overall, major, and very good partial response rates were 84%, 81%, and 19%, respectively. However, the major response rate was lower in those with refractory versus relapsed disease (50% vs 95%; P = .007). Previous exposure to BTK inhibitors was associated with a longer time to response (4.5 vs 1.4 months; P <.001). The median progression-free survival was 30 months.

The only recurring grade 3 or higher treatment-related adverse event was neutropenia, which occurred in 45% of the subjects. No deaths have occurred in the study.

Source: 

Castillo J, Allan J, Siddiqi T,  et al. Venetoclax in Previously Treated Waldenström Macroglobulinemia. J Clin Oncol. Published online November 18, 2021. doi:10.1200/JCO.21.01194.