Patients with chronic lymphocytic leukemia (CLL) who were older or had comorbidities who were treated with fixed duration ibrutinib plus venetoclax experienced fewer relapses and prolonged progression-free survival (PFS) compared with chlorambucil plus obinutuzumab, according to the results reported in the Journal of Clinical Oncology. The rate of undetectable minimal residual disease (uMRD) was also substantially higher among patients treated with ibrutinib plus venetoclax.

The phase 3 GLOW trial ( identifier: NCT03462719) randomly assigned 211 patients with previously untreated CLL who were age 65 or older or who had comorbidities to receive ibrutinib plus venetoclax or chlorambucil plus obinutuzumab. The primary analysis demonstrated a significantly longer PFS with ibrutinib plus venetoclax compared with chlorambucil plus obinutuzumab, which was sustained with a median follow-up of 34.1 months (hazard ratio, 0.212; 95% CI, 0.129-0.349; P <.001). This analysis is uMRD rates and their association with PFS.

uMRD, defined as <10-5 CLL cells leukocytes, was achieved in bone marrow in 40.6% and in peripheral blood in 43.4% of patients treated with ibrutinib plus venetoclax compared with 7.6% and 18.1%, respectively. There were 80.4% of patients in the ibrutinib/venetoclax arm and 26.3% in the chlorambucil/obinutuzumab arm who sustained uMRD for 1 year posttreatment.

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All major subgroups favored ibrutinib plus venetoclax for uMRD at 3 months posttreatment, with no difference according to Rai stage, presence of bulky disease, elevated lactate dehydrogenase at baseline, unmutated IGHV, and presence of del11q.

In the ibrutinib plus venetoclax arm, the PFS at 12 months posttreatment was 96.3% among patients who achieved uMRD in bone marrow and 93.3% for those with uMRD in peripheral blood compared with 83.3% and 58.7%, respectively, in the chlorambucil plus obinutuzumab arm.

The 30-month PFS was 80.5% with ibrutinib plus venetoclax and 35.8% with chlorambucil plus obinutuzumab.

“In conclusion, patients with previously untreated CLL treated with fixed-duration ibrutinib plus venetoclax are less likely to progress clinically during the first year posttreatment, irrespective of their MRD status at 3 months end of treatment and IGHV status, compared with patients treated with chlorambucil plus obinutuzumab,” the authors wrote in their report.

Disclosures: This research was supported by Janssen Research & Development, LLC. Please see the original reference for a full list of disclosures.


Munir T, Moreno C, Owen C, et al. Impact of minimal residual disease on progression-free survival outcomes after fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in the GLOW study. J Clin Oncol. Published online June 6, 2023. doi: 10.1200/JCO.22.02283.