VISION/HO141: Long-term follow-up of MRD-guided treatment with ibrutinib and venetoclax in R/R CLL

Fixed-duration treatment with BTKi or BCL-2 inhibitors may result in undertreatment or early relapses, while continuous treatment leads to cumulative toxicity in R/R CLL. Results of the phase II VISION/HO141 trial (NCT03226301) evaluating the efficacy and safety of MRD-guided ibrutinib and venetoclax cessation and treatment re-initiation in R/R CLL were published by Neiman et al. in Blood Advances.¹

Eligible patients received 15 cycles (28 days each) of oral ibrutinib 420 mg once daily; oral venetoclax was added from D1 of C3. Patients with uMRD were randomized 1:2 to receive ibrutinib maintenance (Arm A, n = 24) and treatment cessation (Arm B, n = 48). Patients who did not achieve uMRD continued ibrutinib maintenance (Arm C, n = 116). The primary endpoint was PFS, defined as the time from enrollment to PD or death. Key secondary endpoints included MRD levels, time to treatment re-initiation and treatment failure, OS, ORR, and safety. 

Key learnings

The median follow-up was 51.7 months. In the ITT population, the 4-year PFS and OS were 81% and 88%, respectively, with next-line treatment required in 14% of patients. 

In the landmark analysis from C15 time of randomization, no difference was observed in OS, PFS, or next-line treatment requirement between treatment cessation, ibrutinib maintenance, or dMRD4-arm continuing ibrutinib.

Lower rates and grades of toxicity were observed in the treatment cessation arm vs ibrutinib maintenance. At the end of C15, patients in Arm B experienced lower rates of infections vs Arms A and C (31% vs 63% and 55%, respectively). 

MRD-guided cessation and re-initiation of ibrutinib plus venetoclax is feasible, improving PFS rates and reducing toxicity vs continuous treatment for patients with R/R CLL. Additionally, this MRD-guided approach may enhance treatment adherence and reduce treatment discontinuations.