Long-term follow-up data indicate that zanubrutinib provided durable responses in patients with Waldenström macroglobulinemia (WM). Tolerability and safety also remained favorable, with most treatment-emergent adverse events (TEAEs) decreasing over time with ongoing treatment. The analysis from the ASPEN trial was presented at the ASH Annual Meeting.
“BTK inhibitors (BTKIs) have become a standard of care for WM,” wrote the authors, led by Shirley D’Sa, MD, of the Centre for Waldenström’s Macroglobulinemia and Associated Disorders at the University College London Hospital Foundation Trust, United Kingdom. The ASPEN study compared outcomes with zanubrutinib versus ibrutinib (N = 129). The current presentation offered outcomes among patients who received zanubrutinib in the ASPEN study and were evaluated as part of a long-term extension (N = 75). The extension required safety assessments every three months and disease-response assessments at least every six months.
As of data cutoff for analysis, median treatment duration during the extension was 23.8 months (range, 0.4–29.4); overall (ASPEN plus extension), it was 73.6 months (range, 49.2–84.2).
During the extension, grade ≥3 TEAEs occurred in 28% of patients and serious TEAEs in 23%. Three patients died (cardiac failure, fall/subdural hematoma, and colorectal cancer).
TEAEs did not lead to treatment discontinuation, but three patients had dose reductions. Grade 3 or higher neutropenia, hypertension, thrombocytopenia, anemia, and back pain occurred less frequently in the extension than in the ASPEN trial.
“Except for second malignancies (skin and non-skin cancer) … the prevalence of TEAEs of interest for BTKis, including neutropenia, decreased over time,” the authors wrote, specifically citing atrial fibrillation/flutter and hypertension.
In ASPEN, overall response rate (ORR) in patients with MYD88-mutated WM was 96.1%, and their rate of very good partial response or better (VGPR+) was 40.2% (versus 95.1% and 36.3%, respectively). In patients with confirmed MYD88-wild type WM, ORR was 84.6%, and VGPR+ was 30.8% (versus 80.8% and 30.8%, respectively). Median durations of response were 55.7 months and 41.1 months, respectively.
As of mid-April 2024, the authors reported that 69.3% (52 of 75) of patients with WM remained on Zanubrutinib.
https://ash.confex.com/ash/2024/webprogram/Paper199276.html
Reference
D’Sa S, Dimopoulos MA, Jurczak W, et al. Long-term clinical outcomes in patients with Waldenström macroglobulinemia (WM) who received zanubrutinib in the phase 3 ASPEN Study: a report from the zanubrutinib extension study. Abstract #3031. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7–10, 2024; San Diego, California.
