Most anticipated studies on chronic lymphocytic leukemia at ASH

This article was originally published on Healio

In this Guest Commentary, Ryan W. Jacobs, MD, principal investigator of clinical trials for chronic lymphocytic leukemia at Atrium Health’s Levine Cancer Institute, reviews studies on CLL that will be presented at the ASH Annual Meeting and Exposition. The most anticipated trials will reveal new information on BTK plus BCL-2 inhibition, updates on major clinical trials — including the CLL14 and MURANO trials — early data on CAR T-cell therapy, and more.

There are a lot of studies updating us on new treatment options for CLL, which is not surprising given how rapidly the field has been progressing. Essentially all the major newer drugs being used to treat CLL have some significant updates. There is also a lot to be excited about regarding where the field may be progressing to in terms of chemotherapy-free small molecule inhibitor combinations that are administered over a defined timeline, produce deep remissions and are well tolerated. This will be a review of the notable oral presentations in CLL.

BTK plus BCL-2 inhibition

There has been evidence and recognition for a while now that using both BTK and BCL-2 inhibition together makes sense in terms of complimentary mechanisms of action, the potential to reduce possible mechanisms of resistance, and how well these drugs treat disease in different sanctuaries of the body. For example, ibrutinib (Imbruvica; Pharmacyclics, Janssen), a BTK inhibitor, targets disease well in the enlarged lymph nodes and spleen. Venetoclax (Venclexta; AbbVie, Genentech) is really good at clearing out the circulating disease quite rapidly.

There are five noteworthy oral presentations evaluating the combination of BCL-2 inhibition and BTK inhibition. The most significant in terms of the number of patients on the trial and the length of follow up is the phase 2 CAPTIVATE study (Tam CS, et al. Abstract 35), which looked at the combination of ibrutinib plus venetoclax for 1 year after a 3-month lead-in with ibrutinib (I acknowledge I may be biased as I am a contributing author). The study enrolled 164 patients aged younger than 70 years, which is more than double the number of patients compared with the other oral presentations that are investigating this combination. CAPTIVATE is also unique in that it is not restricted to high-risk patients, which one of the other trials specifically focuses on. This trial looked at MRD negativity in both the peripheral blood and the bone marrow at the end of 1-year combined therapy. That is the information that is going to be reported because the median follow up is only 14.7 months so far, which is not long enough to fully analyze PFS data. The combination seems to be very effective — close to a 100% overall response rate. At the 1-year mark of combined therapy, the highest reported rates of bone marrow MRD negativity was 71%. The concordance rate between MRD negativity and peripheral blood was very high at 93%. This means that most of the patients who were MRD negative in the blood were also MRD negative in the bone marrow.

Read more from the study here