Venetoclax-Ibrutinib Demonstrates Long-Term Efficacy Among Patients With R/R Mantle Cell Lymphoma

Phase 2 Results from the AIM Study

According to long-term results from a phase 2 clinical trial, venetoclax-ibrutinib treatment for patients wtih relapsed/refractory (R/R) mantle cell lymphoma (MCL) demonstrated durable responses and an acceptable toxicity profile, as well as the feasibility of treatment interruption while still maintaining ongoing disease control.

In the AIM trial, 24 patients with MCL (23 with R/R disease) received ibrutinib 560 mg and venetoclax 400 mg both once daily. Investigators noted high complete remission (CR), and measurable residual disease negative (MRD-negative) CR rates were previously reported. Treatment was initially continuous, with elective treatment interruption allowed only after protocol amendments for patients in MRD-negative CR.

Study results demonstrated among patients with R/R MCL, the estimated 7-year progression-free survival (PFS) was 30% (95% confidence interval [CI], 14 to 49; median, 28 months; 95% CI, 13 to 82) and overall survival (OS) was 43% (95% CI, 23 to 62; median, 32 months; 95% CI, 15 to not evaluable). Furthermore, 8 patients in MRD-negative CR entered ETI for a median of 58 months (95% CI, 37 to 79), with 4 patients experiencing disease recurrence. Investigators noted 2 out of 3 participants reattained CR on retreatment.

The time-to-treatment failure (TTF), which excluded progression in elective treatment interruption for those reattaining response, was 39% overall and 68% at 7 years for responders. Beyond 56 weeks, researchers noted that grade ≥3 and serious adverse events were uncommon. Additionally, newly emergent or increasing cardiovascular toxicity were not observed beyond 56 weeks.

 “We demonstrate long-term durable responses and acceptable toxicity profile of venetoclax-ibrutinib in R/R MCL and show feasibility of treatment interruption while maintaining ongoing disease control,” concluded lead study author Sasanka Handunnetti, MBBS, PhD, Peter MacCallum Cancer Center, Melbourne, Australia, and colleagues.

Source:

Handunnetti S, Anderson MA, Burbury K, et al. Seven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: Durable responses and treatment-free remissions. Blood. Published online August 22, 2024. doi: 10.1182/blood.2023023388