Seven-Year Follow-Up Confirms Durable Remissions with Venetoclax-Ibrutinib in Mantle Cell Lymphoma
With median follow-up exceeding 7 years in the AIM phase 2 trial, venetoclax-ibrutinib achieved 30% estimated 7-year PFS and 43% OS in relapsed/refractory MCL. Eight patients in MRD-negative complete remission entered elective treatment interruption for a median of 58 months, with four experiencing recurrence. The data demonstrate that MRD-guided treatment cessation is feasible while maintaining long-term disease control.
The original study
Seven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: durable responses and treatment-free remissions.
- Authors
- Handunnetti SM, Anderson MA, Burbury K, Thompson PA, Burke G, Bressel M, et al.
- Journal
- Blood
- Type
- Journal Article, Clinical Trial, Phase II, Multicenter Study, Research Support, Non-U.S. Gov't
- PMID
- 38662991
Original abstract
In the phase 2 clinical trial (AIM) of venetoclax-ibrutinib, 24 patients with mantle cell lymphoma (MCL; 23 with relapsed/refractory [R/R] disease) received ibrutinib 560 mg and venetoclax 400 mg both once daily. High complete remission (CR) and measurable residual disease negative (MRD-negative) CR rates were previously reported. With median survivor follow-up now exceeding 7 years, we report long-term results. Treatment was initially continuous, with elective treatment interruption (ETI) allowed after protocol amendment for patients in MRD-negative CR. For R/R MCL, the estimated 7-year progression-free survival (PFS) was 30% (95% confidence interval [CI], 14-49; median, 28 months; 95% CI, 13-82) and overall survival (OS) was 43% (95% CI, 23-62; median, 32 months; 95% CI, 15 to not evaluable). Eight patients in MRD-negative CR entered ETI for a median of 58 months (95% CI, 37-79), with 4 experiencing disease recurrence. Two of 3 reattained CR on retreatment. Time-to-treatment failure (TTF), which excluded progression in ETI for those reattaining response, was 39% overall and 68% at 7 years for responders. Beyond 56 weeks, grade ≥3 and serious adverse events were uncommon. 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. This trial was registered at www.clinicaltrials.gov as #NCT02471391.