A new opportunity for the treatment of patients with relapsed chronic lymphocytic leukemia: results from a Swiss study
Institute of Oncology Research
The Experimental Hematology Lab research group, led by Prof. Davide Rossi at the Institute of Oncology Research (IOR, affiliated to USI and member of Bios+), has discovered that the an oral combination of ibrutinib and venetoclax for 2 years increases the chances of getting a very deep response and that treatment with the ibrutinib and venetoclax combination has been shown to be safe and effective, also for patients whose CLL comes back after a long period of remission.
The study is published in Blood, the flagship journal of the American Society of Hematology.
Background
Chronic lymphocytic leukemia (CLL) is a type of cancer that affects a type of white blood cell called lymphocytes, which help fight infections. Patients with CLL have many of these abnormal lymphocytes in the blood, bone marrow, lymph nodes and spleen. CLL usually develops slowly and might not cause symptoms at first, but over time, it can lead to fatigue, frequent infections, anemia, lymph node or spleen enlargement.
Venetoclax and ibrutinib are medicines used to treat CLL. They work in different ways to help stop the leukemia cells from growing. Ibrutinib blocks signals that CLL cells need to survive, helping to slow down or stop their growth. Venetoclax helps cause leukemia cells to die by targeting a protein that keeps them alive. Both drugs are taken by mouth. They have made a big difference in how CLL is treated and can help many people live longer and feel better.
The discovery
The combination of ibrutinib and venetoclax is being used to treat CLL because the two medicines work in different but complementary ways to fight the cancer. In studies, treatment usually starts with a short period of ibrutinib alone, followed by adding venetoclax for about 12 months. The study from the Swiss Group for Clinical Cancer Research (called SAKK 34/17) is a prospective clinical trial that tested a slightly different approach to give treatment with venetoclax and ibrutinib in patients whose CLL has come back or stopped responding to treatment. Key findings of the clinical trial are:
Starting with ibrutinib alone for a longer time helps lower risks: By giving ibrutinib by itself for 6 months before adding venetoclax, treatment can gradually shrink the leukemia. This helps reduce the chance of a serious complication called tumor lysis syndrome, which can happen when cancer cells break down too quickly and release harmful substances into the blood.
Longer treatment with both drugs improves results: Keeping patients on the combination of ibrutinib and venetoclax for 2 years increases the chances of getting a very deep response—meaning the cancer is no longer detectable in the blood using very sensitive tests. This is known as undetectable minimal residual disease and is linked to better long-term outcomes.
Blood test using tumor DNA didn’t add new information: Researchers also looked at whether a special blood test that detects leftover cancer DNA (called circulating tumor DNA or ctDNA) could give more insights. However, this test did not show any clear advantage over existing methods that use high-tech tools to measure tiny amounts of cancer through immune system markers (a method called immunoglobulin high-throughput sequencing for MRD testing).
Outlook
Treatment with the ibrutinib and venetoclax combination has been shown to be safe and effective, also for patients whose CLL comes back after a long period of remission. Since the ibrutinib-venetoclax treatment is taken entirely by mouth and only given for a limited time, it’s often easier and more convenient for patients compared to combinations like venetoclax with rituximab, which requires intravenous infusions. Plus, the ibrutinib and venetoclax combination offers similar benefits in terms of how long the cancer stays under control, making it a good option for people with relapsed CLL. These results also contribute to the increasing body of evidence supporting the idea that a longer ibrutinib and venetoclax combination duration is beneficial for enhancing therapeutic effectiveness
The study
“Ibrutinib lead-in followed by venetoclax plus ibrutinib for relapsed/refractory chronic lymphocytic leukemia: the SAKK 34/17 trial”: https://www.sciencedirect.com/science/article/pii/S000649712500477X?dgcid=author
