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TOPLINE:

Measurable residual disease-guided ibrutinib-venetoclax therapy achieved undetectable disease in bone marrow in 66.2% of patients with chronic lymphocytic leukemia (CLL) within 2 years compared with none with ibrutinib alone and 48.3% with fludarabine, cyclophosphamide, and rituximab (FCR). With a median follow-up of 62.2 months, progression-free survival at 5 years reached 93.9% with ibrutinib-venetoclax vs 79.0% with ibrutinib alone and 58.1% with FCR.

METHODOLOGY:

• A phase 3, multicenter, open-label, parallel-group, randomized, controlled, adaptive trial platform recruited participants from 99 hospitals in the UK.
• Participants aged 18-75 years with previously untreated CLL or small lymphocytic lymphoma requiring treatment were randomized in a 1:1:1 ratio to receive ibrutinib-venetoclax, ibrutinib alone, or fludarabine-cyclophosphamide-rituximab.
• Treatment protocols included FCR, repeated every 28 days for six cycles, while ibrutinib was administered orally at 420 mg daily.
• The ibrutinib-venetoclax group received ibrutinib for 8 weeks before initiating venetoclax, which was administered orally at up to 400 mg daily with incremental dose escalation over 5 weeks.

TAKEAWAY:

• Measurable residual disease was undetectable in bone marrow within 2 years in 66.2% (172/260) of ibrutinib-venetoclax participants compared with none in the ibrutinib-alone group and 48.3% (127/263) in the FCR group (P < .001).
• Disease progression or death occurred in 6.9% (18/260) of ibrutinib-venetoclax participants vs 22.4% (59/263) in the ibrutinib-alone group (hazard ratio [HR], 0.29; 95% CI, 0.17-0.49; P < .001) and 42.6% (112/263) in the FCR group (HR, 0.13; 95% CI, 0.08-0.21; P < .001).
• Five-year progression-free survival rates were 93.9% with ibrutinib-venetoclax, 79.0% with ibrutinib alone, and 58.1% with FCR.
• Death rates were 4.2% (11/260) in the ibrutinib-venetoclax group vs 9.9% (26/263) in the ibrutinib-alone group (HR, 0.41; 95% CI, 0.20-0.83) and 14.8% (39/263) in the FCR group (HR, 0.26; 95% CI, 0.13-0.50).

IN PRACTICE:

“Among patients with CLL, undetectable MRD and extended progression-free survival were more common with MRD-guided ibrutinib-venetoclax treatment than with ibrutinib alone or FCR, and the results for overall survival were also consistent with a benefit of MRD-guided ibrutinib-venetoclax (especially among those with unmutated IGHV), findings that support individualized therapy on the basis of response in real time,” wrote the authors of the study.

SOURCE:

The study was led by researchers from the Leeds Cancer Research UK Clinical Trials Unit at the University of Leeds, with laboratory analysis performed at the Haematological Malignancy Diagnostic Service, St. James’s University Hospital in Leeds, England. It was published online on June 15 in The New England Journal of Medicine.

LIMITATIONS:

According to the authors, the findings should be interpreted in the context of the relatively young trial population, where longer-term follow-up is essential to evaluate the potential for functional cure.

DISCLOSURES:

The study was supported by grants from Cancer Research UK, with additional unrestricted educational grants from Johnson & Johnson, Pharmacyclics, and AbbVie for trial coordination and laboratory studies. Cancer Research UK also provided a grant for Core Clinical Trials Unit Infrastructure.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.