Venetoclax and delayed rituximab with ibrutinib consolidation aiming at undetectable minimal residual disease (uMRD) in treatment-naïve patients with chronic lymphocytic leukemia (CLL)

Clinical study for the treatment of chronic lymphocytic leukemia (CLL) based on a minimal residual disease (MRD)-guided approach, aimed at personalizing treatment intensity according to disease response. 
The drugs used will include the antibody Rituximab, in combination with Venetoclax, a BCL-2 protein inhibitor approved for use in CLL. Following an initial phase of Venetoclax monotherapy, patients showing an early response will be identified. The subsequent addition of Rituximab after 6 months is expected to enhance the depth of response, by administering the antibody at a time of lower disease burden, with the goal of achieving a higher rate of undetectable minimal residual disease (uMRD) compared to the typical upfront combination of both therapies. 

Patients who achieve uMRD in peripheral blood, confirmed by repeat assessments, will then undergo bone marrow testing. If MRD is also undetectable in the bone marrow, and after a total of 12 months of Venetoclax therapy (including 6 months of Rituximab), treatment may be discontinued. 

Patients with detectable MRD will add Ibrutinib at the standard dose of 420 mg once daily, continuing until MRD becomes undetectable, or until disease progression or unacceptable toxicity. Additionally, Venetoclax treatment may continue for as long as MRD remains detectable, up to a maximum of 24 months. 

This approach will allow for treatment intensification in patients who need it, while sparing toxicity and preserving treatment options in those who have already achieved deeper responses.