Talha Munir, MD, St James's Hospital, Leeds, United Kingdom, discusses findings from an updated interim analysis of the FLAIR study, which were presented at the 2022 ASH Annual Meeting & Exposition in New Orleans, LA.

The study revealed that the combination of BTK inhibitor ibrutinib plus venetoclax led to high rates of MRD negativity in both patients with IGHV-mutated and IGHV-unmutated CLL, though those with IGHV-unmutated CLL were statistically more likely to achieve MRD negativity than those with IGHV-mutated CLL.

Transcript: 

Hi, I'm Dr. Talha Munir. I'm a hematology consultant working at St James's Hospital in Leeds, UK. It's my pleasure to be here in New Orleans attending the ASH conference. I'm really excited to share the data on FLAIR study, which I presented today in the CLL session.

Briefly, the FLAIR study showed an adaptive trial design where we showed the data of ibrutinib comparison to ibrutinib with venetoclax in terms of the primary endpoint analysis. We had 50% of the patients who've reached that endpoint, so I presented the data on the combination. The primary endpoint of the study was MRD negativity, and majority of the patients in the ibrutinib with venetoclax arm achieved that. So our MRD-negative rates were about 65.4% in the bone marrow, and extending to around 72% in the peripheral blood.

What we interestingly found in this study was the patients who had unmutated IGHV status were benefiting the most from the ibrutinib venetoclax combination, and they were achieving their MRD-negative rates in around 80% of the patients. Also of note was that the median time to achieve MRD negativity was much shorter in the IGHV-unmutated arm as compared to the mutated IGHV patients.

In short, the FLAIR study in this adaptive trial design is showing us that with a short-term endpoint of MRD negativity, ibrutinib and venetoclax is very good in achieving that in unmutated IGHV patients, and some other genetic profile patients such as ATM-deleted patients were benefiting the most from this combination.

Source:

Munir, T, Pitchford A, Bloor A, et al. Combination of Ibrutinib Plus Venetoclax with MRD-Driven Duration of Treatment Results in a Higher Rate of MRD Negativity in IGHV Unmutated Than Mutated CLL: Updated Interim Analysis of FLAIR Study. Presented at the ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA, and virtual. Abstract 94.