Undetectable MRD on maintenance venetoclax, acalabrutinib, and obinutuzumab in the majority of R/R CLL participants

Ongoing maintenance therapy with venetoclax, acalabrutinib, and obinutuzumab resulted in an undetectable minimal residual disease (MRD) rate of 93.3% in participants with relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL), an analysis of the phase 2 CLL2-BAAG trial showed.

The phase 2 CLL2-BAAG trial (NCT03787264) tested a regimen of acalabrutinib, venetoclax, and obinutuzumab in 45 participants with R/R CLL. In a previous analysis of that study, 76% of the participants achieved an undetectable MRD after induction therapy [1]. Dr Moritz Fürstenau (University of Cologne, Germany) presented the follow-up efficacy data [2].

In 7 out of 10 participants with detectable MRD after induction therapy, undetectable MRD was reached during maintenance therapy. Therefore, the undetectable MRD rate was 93.3% and the median time to undetectable MRD was 5.4 months. “The MRD approach helps us to see which patients could benefit from prolonged treatment because not all patients achieve undetectable MRD at the same time,” added Dr Fürstenau. The 30-month progression-free survival and overall survival rates were 88.2% and 100%, respectively. Furthermore, ctDNA was detected before MRD positivity in 3 out of a total number of 5 progressing participants. Finally, earlier molecular relapse identification by ctDNA was seen in participants with more dynamic diseases, those with genetic high-risk features, and those with more advanced diseases.

“The progression-free survival and overall survival rates observed are comparable with established treatment options in the R/R setting. Yet, with maintenance venetoclax, acalabrutinib and obinutuzumab, rates were achieved with a shorter median treatment duration of 14.7 months as compared with approximately 24 months for participants on a venetoclax-rituximab regimen alone,” highlighted Dr Fürstenau.

In conclusion, in the current phase 2 CLL2-BAAG study MRD-guided venetoclax plus acalabrutinib, and obinutuzumab resulted in deep and durable remission in a population of participants with CLL who had received prior BTK inhibitor and/or venetoclax treatment. Also, ctDNA-based analyses, added to standard flow cytometry MRD, may enhance early detection of molecular relapses.

1. Cramer P, et al. Lancet Haematol. 2022;9(10):e745-e755.
2. Fürstenau M, et al. Long-term Remissions with MRD-guided acalabrutinib, venetoclax, and obinutuzumab in relapsed/refractory CLL: follow-up efficacy and ctDNA analysis of the CLL2-BAAG trial. Abstract 203, 65^th ASH Annual Meeting, 9–12 December 2023, San Diego, CA, USA.

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Posted on 7 February 2024