A new clinical trial shows that patients with chronic lymphocytic leukemia (CLL) achieve similar outcomes whether they receive continuous single-agent therapy or a fixed-duration combination treatment.
This is the first prospective study to directly compare these two treatment strategies. After a median follow-up of nearly three years, the risk of disease progression or death was comparable across both approaches.
CLL, the most common adult leukemia, is characterized by the uncontrolled growth of abnormal white blood cells in the bone marrow. Treatments target the disease using three classes of drugs: Bruton tyrosine kinase (BTK) inhibitors, BCL2 inhibitors, and CD20 antibodies. Standard regimens for newly diagnosed patients include indefinite BTK inhibitor therapy or fixed-duration combination therapy lasting roughly a year.
In the trial, 909 adults were randomly assigned to one of three treatment arms. Patients in the “I” arm received continuous ibrutinib (a BTK inhibitor) until disease progression or unacceptable side effects. The “VO” arm received 12 cycles of venetoclax (a BCL2 inhibitor) combined with obinutuzumab (a CD20 antibody) for the first six cycles. The “VI” arm received 12 cycles of venetoclax following three cycles of ibrutinib.
After a median follow-up of 34 months, progression-free survival was 81% in the I arm, 81.1% in the VO arm, and 79.4% in the VI arm. These differences were below the pre-specified threshold for non-inferiority, meeting the study’s primary endpoint.
Overall response rates ranged from 84.2% to 88.5%, and overall survival ranged from 91.5% to 96.0%, showing similar outcomes across all groups. However, continuous ibrutinib therapy resulted in lower rates of complete response (8.3% versus 51.5% in VO and 46.2% in VI) and did not achieve undetectable measurable residual disease (MRD), a marker of minimal remaining cancer cells. By contrast, MRD negativity was reached in 73% (VO) and 62% (VI) of patients in blood samples, and 62% (VO) and 40% (VI) in bone marrow samples.
“The secondary endpoints give us an indication of long-term efficacy,” said Dr. Al Sawaf. “Fixed-duration therapy shows higher complete response and MRD rates, while continuous single-agent therapy shows lower rates.”
Side effect rates were similar across the groups, most commonly infections and gastrointestinal issues, along with blood, cardiac, and secondary cancer concerns. Cardiovascular problems were more frequent among patients on long-term ibrutinib, while obinutuzumab was linked to a higher risk of severe infections and shorter progression-free survival in aggressive CLL cases.
Researchers noted that ongoing follow-up will further clarify differences between the treatments. Dr. Al Sawaf also highlighted ongoing studies to identify biomarkers that could help tailor therapy to individual patients.
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