The combination of ibrutinib and venetoclax was found to provide lasting disease remission in patients with newly diagnosed chronic lymphocytic leukemia (CLL). Findings from a single-institution phase II study were published by Nitin Jain, MD, and colleagues in JAMA Oncology and provide the longest follow-up data on patients treated with this drug regimen.
Researchers previously reported results from this study in 2019 in The New England Journal of Medicine, showing that ibrutinib and venetoclax were effective when given together for high-risk and older patients with the disease. This report offers an additional 2 years of follow-up data and statistics on bone marrow undetectable measurable residual disease (U-MRD) after treatment.
Overall, the 3-year progression-free survival was 93% and the 3-year overall survival was 96%. The response rates were the same for the high-risk subgroup of patients.
Nitin Jain, MD
“CLL is the most common leukemia in the United States and was originally treated with chemoimmunotherapy,” said Dr. Jain. “These long-term results show that 2 years of oral targeted therapy can achieve lasting disease remission for patients with CLL.”
Study Details
Researchers followed 80 previously untreated patients with a median age of 65 years, 30% of whom were over age 70. Overall, 92% had high-risk genetic anomalies. The median follow-up for all 80 patients was 38.5 months. Trial participants were 94% White, 4% other, 1% American Indian or Alaska Native, and 1% unknown.
The U-MRD responses improved with ongoing combined ibrutinib plus venetoclax. After 12 cycles of combination therapy, 56% of patients achieved bone marrow U-MRD, and after 24 cycles of combination therapy, 66% of patients achieved bone marrow U-MRD remission. A total of 75% of patients achieved bone marrow U-MRD remission at any time during the study.
“MRD is one of the most important prognostic markers at the end of leukemia treatment,” said Dr. Jain. “The majority of patients achieved bone marrow MRD remission and no patients on the trial had CLL disease progression.”
The treatment was well tolerated and the toxicity profile of both drugs was consistent with other studies, with no additional toxicity observed with the combination.
The research team continues to monitor the patients’ MRD every 6 months and is working on further correlative studies.
“I think this will be one of several standard of care treatments available for patients with CLL,” Dr. Jain said. “There are pros and cons to each of those approaches, and physicians will have to decide which option is best for their patient.”
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
