The following is a summary of “Impact of Minimal Residual Disease on Progression-Free Survival Outcomes After Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study,” published in the July 2023 issue of Oncology by Munir, et al.

In the GLOW study, the combination of fixed-duration ibrutinib and venetoclax demonstrated superior progression-free survival (PFS) compared to chlorambucil and obinutuzumab in older or comorbid patients with previously untreated chronic lymphocytic leukemia (CLL). For a study, researchers sought to investigate the kinetics of minimal residual disease (MRD) and its potential predictive value for PFS, as it had not been evaluated in the context of ibrutinib and venetoclax treatment.

Undetectable MRD (uMRD) was assessed using next-generation sequencing, with thresholds set at <1 CLL cell per 10,000 (<10^-4) and <1 CLL cell per 100,000 (<10^-5) leukocytes. PFS was analyzed based on MRD status at 3 months after treatment (end of treatment plus 3 months, (EOT+3).

The combination of ibrutinib and venetoclax achieved deeper rates of uMRD (<10^-5) in bone marrow (BM) and peripheral blood (PB) in 40.6% and 43.4% of patients, respectively, at EOT+3, compared to 7.6% and 18.1% of patients receiving chlorambucil and obinutuzumab. Among these patients, uMRD (<10^-5) in PB was sustained during the first year post-treatment (EOT+12) in 80.4% of patients receiving ibrutinib and venetoclax, and 26.3% receiving chlorambucil and obinutuzumab. Patients with detectable MRD (dMRD; ≥10^-4) in PB at EOT+3 were more likely to sustain MRD levels through EOT+12 with ibrutinib and venetoclax compared to chlorambucil and obinutuzumab. PFS rates at EOT+12 were high among patients treated with ibrutinib and venetoclax regardless of MRD status at EOT+3: 96.3% and 93.3% in patients with uMRD (<10^-4) and dMRD (≥10^-4) in BM, respectively, versus 83.3% and 58.7% for patients receiving chlorambucil and obinutuzumab. PFS rates at EOT+12 also remained high in patients with unmutated immunoglobulin heavy-chain variable region (IGHV) receiving ibrutinib and venetoclax, independent of MRD status in BM.

Patients treated with ibrutinib and venetoclax experienced fewer molecular and clinical relapses during the first year post-treatment compared to those receiving chlorambucil and obinutuzumab, regardless of MRD status at EOT+3 and IGHV status. Even in patients not achieving uMRD (<10^-4), PFS rates remained high with ibrutinib and venetoclax, suggesting potential long-term efficacy that requires further follow-up confirmation.

Source: ascopubs.org/doi/full/10.1200/JCO.22.02283