Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
Treatment with ibrutinib–venetoclax produced high rates of uMRD and durable progression-free survival in patients with CLL, irrespective of lymph node size. Patients with bulky lymph nodes at baseline were less likely to have them shrink back to normal size after treatment with ibrutinib-venetoclax, but this did not affect their long-term survival outcomes.
Who Performed the Research and Where Was it Presented:
Dr. Constantine Tam from Alfred Hospital and Monash University and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2024.
Background:
Enlarged lymph nodes are one of the clinical symptoms of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Patients with CLL/ SLL responses to therapy are assessed using iwCLL criteria, which has several components, including lymph node size. The lymph nodes have to shrink back to ≤1.5 cm in diameter for a response to be considered a complete response. However, in the era of targeted therapies and undetectable measurable residual disease (uMRD) testing, it is unclear how lymph node size relates to patient outcomes like progression-free survival.
The CAPTIVATE study was the first large clinical trial to test the combination of ibrutinib and venetoclax as a first-line treatment for CLL / SLL. It was an all-oral combination therapy given for a fixed duration over time and was very effective. At four years of follow-up, the progression-free survival rate was 79%. In this exploratory analysis, researchers looked at whether baseline lymph node size or lymph node size at the end of treatment was related to patient outcomes.
Methods and Participants:
This was a phase 2 clinical trial in patients ≤70 years of age with previously untreated CLL / SLL. Patients received three cycles of ibrutinib followed by 12 cycles of ibrutinib plus venetoclax for a total treatment period of approximately 15 months. For this analysis, patients were categorized as having either bulky lymph nodes (≥5 cm) or non-bulky lymph nodes (<5 cm).
Results:
- The CAPTIVATE trial now has a median of 5.5 years of follow-up with 202 patients completing fixed-duration ibrutinib-venetoclax treatment.
- 33% of patients had bulky lymph nodes.
- At the end of treatment, 65% of patients with non-bulky lymph nodes and 77% of patients with bulky lymph nodes had achieved uMRD in the peripheral blood.
- Progression-free survival was 67% for patients with non-bulky lymph nodes and 63% for patients with bulky lymph nodes.
- Overall survival was 97% for both groups of patients.
- 71% of patients with non-bulky lymph nodes had them shrink to ≤1.5 cm by the end of treatment, but this only happened for 27% of patients with bulky lymph nodes.
- Progression-free survival rates were high (75%) in patients with uMRD regardless of lymph node size.
Conclusions:
Treatment with ibrutinib-venetoclax produced high rates of uMRD and durable progression-free survival. Patients with bulky lymph nodes at baseline were less likely to have them shrink back to normal size after treatment with ibrutinib-venetoclax, but this did not affect their long-term survival outcomes. Dr. Sharman has used the analogy that when you blow up a balloon and let the air out, it never shrinks to its original size. When these slightly enlarged nodes are biopsied, they often show no CLL, just some excess scar tissue. Long-term progression-free survival was most strongly associated with uMRD status. Depth of response (complete remission vs. partial remission) only had a minor impact. This study highlights that MRD testing is a much more meaningful way of evaluating disease burden in CLL compared with traditional imaging methods such as lymph node size. While MRD testing has been limited to clinical trials, hopefully, with time, it will make its way into clinical practice.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Consistently High 5.5-Year Progression-Free Survival (PFS) Rates in Patients with and without Bulky Baseline Lymphadenopathy ≥5 Cm Are Associated with High Undetectable Minimal Residual Disease (uMRD4) Rates after First-Line Treatment with Fixed-Duration Ibrutinib + Venetoclax for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) in the Phase 2 CAPTIVATE Study
