Venetoclax Consolidation Therapy Increased Achievement of Undetectable MRD Among Patients With High-Risk CLL

The addition of venetoclax therapy among patients with high-risk chronic lymphocytic leukemia (CLL) who had received at least 12 months or more of ibrutinib treatment achieved a high rate of undetectable measurable residual disease (U-MRD) in the bone marrow, according to a study published in Leukemia. These findings demonstrate this treatment combination’s potential for durable treatment-free remission. 

“Patients receiving ibrutinib for CLL rarely achieve undetectable measurable residual disease, necessitating indefinite therapy, with cumulative risks of treatment discontinuation due to progression or adverse events,” Philip A Thompson, MD, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, and coauthors stated. The study authors aimed to assess the possible impact of adding venetoclax, a BCL-2 inhibitor, to ibrutinib therapy among patients with CLL and one or more high-risk features. 

This study enrolled 45 patients with CLL who had received ibrutinib for ≥12 months and had high-risk features, such as TP53 mutation and/or deletion, ATM depletion, complex karyotype, or persistently elevated β2-microglobulin. The primary end point was the measurement of U-MRD with 10–4 sensitivity (U-MRD4) in the bone marrow at 12 months. 

Based on intention-to-treat analysis, 55% of the patients (n = 23) showed an improved response, achieving complete remission after venetoclax was added to the ibrutinib regimen. Notably, 2 patients already exhibited MRD-positive complete response at the initiation of venetoclax. At 12 months, U-MRD4 in the bone marrow was observed in 57% of patients. After the completion of venetoclax treatment, 71% of patients (n = 32) achieved U-MRD. Among these patients, 22 discontinued ibrutinib treatment, and 10 continued with the ibrutinib treatment. 

At a median follow-up of 41 months from the initiation of venetoclax, 5 out of 45 patients experienced disease progression. There were no patient deaths as a result of CLL or Richter Transformation at time of follow-up. Among 32 patients who achieved bone marrow U-MRD4, peripheral blood MRD4 was assessed every 6 months. At a median of 13 months after venetoclax treatment, 10 patients out of the 32 experienced peripheral blood MRD4 re-emergence. 

Dr Thompson et al concluded, “the addition of venetoclax in patients treated with ≥12mo of ibrutinib achieved high rate of [bone marrow] U-MRD4 and may achieve durable treatment-free remission.” 

Source: 

Thompson PA, Keating MJ, Ferrajoli, A. et al. Venetoclax consolidation in high-risk CLL treated with ibrutinib for ≥1 year achieves a high rate of undetectable MRD. Leukemia. Published online May 3, 2023. doi:10.1038/s41375-023-01901-4