In a new study published in the Journal of Clinical Oncology and presented at #ASH24, Matthew Davids, MD, MMSC, of Dana-Farber Cancer Institute, shared promising findings: a time-limited AVO triplet therapy offers durable remission for high-risk CLL patients.
The inspiration for this study came from the high level of activity that we see with acalbrinib and Venetoclaxobintuzumab as separate regimens. And so starting way back in 2017, we designed this study to look at a triplet combination with all three drugs. And over the years, a phase 3 study called Amplify was also developed, which also just read out at the AS meeting and was published. And the Amplify study compared the AVO triplets to an AV doublet and chemo immunotherapy and found that the triplet regimen was beneficial. uh, but unfortunately, the Amplify study excluded patients with high genetic risk CLL, particularly those with TP 53 aberration. So our study, a phase 2 trial of the AVO triplet, actually enriched the population for TP53 aberrant disease. We treated these patients sequentially with these three drugs and then in combination, and all patients received at least 15 cycles of the treatment, and then if they had undetectable minimal residual disease, they could stop therapy. Some patients went on to receive a total of 2 years of therapy and again could stop at the end of the 2 years if they achieved undetectable MRD. In total we recruited 72 patients to our study, and 63% of the population was this high risk TP53 aberrant group. The primary input of the study was the rate of complete remission with undetectable MRD in the bone marrow at cycle 16, and this was achieved both in 42% of the overall population and also in 42% of the patients with TP53 aberration. We also saw high rates of undetectable MRD in the bone marrow in the range of about 78% in the overall population and 71% in those patients with TP 53 aberration. This was a very well tolerated triplet regimen. The rates of cardiovascular and bleeding complications were low, and at a median follow-up of about 55 months now, only 10 patients have progressed. So the 4 year progression free survival, particularly in these patients with TP 53 aberration, is 70%, which does compare favorably with other studies of time-limited regimens such as Venetoclax, or vintuzumab and other studies. So overall we've concluded that AVO is a highly active and well tolerated regimen, particularly in these high genetic risk patients, and we do think this supports its use as a potential new standard of care option for frontline CLL treatment. Although there are ongoing phase 3 trials comparing this AVO triplet to Venetoclaxotuzumab in patients with high risk disease, and we'll await those comparative studies for additional data.
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