Posted: Friday, December 23, 2022
Philip A. Thompson, MBBS, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues hypothesized that by adding venetoclax to ibrutinib therapy, patients with high-risk chronic lymphocytic leukemia (CLL) might achieve undetectable measurable residual disease (MRD) and be able to discontinue treatment. Presented during the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 96), the results of this phase II study concluded this treatment combination was well tolerated.
“Consolidation venetoclax added to ibrutinib in patients with high-risk CLL was well tolerated and achieved [a] cumulative bone marrow–undetectable-MR4 rate of 73%; ibrutinib [was discontinued] in 49% of patients,” concluded the investigators. “At a median of 12 months post-venetoclax follow-up, most patients who attained bone marrow–undetectable MRD have ongoing undetectable MRD in blood.”
The study authors focused on 45 patients with high-risk CLL who previously received at least 1 year of ibrutinib. For up to 24 cycles of 28 days, ibrutinib was continued at 140 to 420 mg daily, and venetoclax escalation was performed to the target dose of 400 mg daily.
Undetectable MRD was achieved in 38% of patients after 6 treatment cycles and in 57% after 12 cycles. Additionally, 57% of patients achieved a complete response to treatment with venetoclax. The median follow-up for progression-free and overall survival was 37.5 and 40.3 months, respectively. A total of 32 participants had undetectable MRD after treatment completion, 10 of whom stopped venetoclax prior to 24 cycles. Upon venetoclax completion, 10 patients with undetectable MRD continued ibrutinib at the physician’s discretion; 5 participants experienced disease progression on or after treatment.
The most common adverse event was grade 1 or 2 diarrhea, and the most common grade 3 or 4 event was neutropenia (20%). Although no patient halted venetoclax treatment due to toxicity, three developed grade 3 infections. Severe adverse events were reported in 17 patients, with the most common being non-melanoma skin cancer (n = 9).
Disclosure: For full disclosures of the study authors, visit ash.confex.com.