iwCLL 2023 | Update on the CLL2-BAAG trial
In this video, Paula Cramer, MD, University of Cologne, Cologne, Germany, presents an update of the Phase II CLL2-BAAG trial (NCT03787264) which investigated the efficacy of a sequential regimen of obinutuzumab, acalabrutinib, and venetoclax, preceded by an optional debulking phase with bendamustine, in a cohort of patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Despite this cohort being pre-treated and considered a high-risk cohort, updated analysis has shown positive outcomes in these patients, with many reaching deep remission. These results were seen even in those patients who had previously been treated with targeted agents (BTK inhibitor and/or venetoclax). This interview was recorded at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2023 meeting, held in Boston, MA.
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Transcript (edited for clarity)
So in my talk this afternoon, I will give an update on the CLL2-BAAG trial, which is a Phase II trial where we evaluate the triple combination of obinutuzumab, acalabrutinib and venetoclax, and we have an optional debulking in the beginning with bendamustine. That’s why we have the B in the beginning of the name. In this trial we treated 45 patients with relapsed CLL. These were rather young and fit patients, but it was a cohort that was enriched for high risk abnormalities...
So in my talk this afternoon, I will give an update on the CLL2-BAAG trial, which is a Phase II trial where we evaluate the triple combination of obinutuzumab, acalabrutinib and venetoclax, and we have an optional debulking in the beginning with bendamustine. That’s why we have the B in the beginning of the name. In this trial we treated 45 patients with relapsed CLL. These were rather young and fit patients, but it was a cohort that was enriched for high risk abnormalities. Two thirds of them? No. Three quarters of them had an unmutated IGVH status and one third had tp53 abnormalities and one third had a complex karyotype. So it’s rather a high risk cohort. And all of them were previously treated. Almost half of them had already received a targeted agent, mainly BTK inhibitors or venetoclax, in some cases also both of them.
In the trial, only 18 of the 45 patients received the bendamustine debulking, and then they received the induction treatment with the triple combination, which started with the obinutuzumab for one cycle as a single agent, then the Acalabrutinib was added, and in the third cycle the venetoclax ramp up started. So after six cycles of the combination treatment, we have the final staging, which was the primary endpoint of the trial. And at that time point 13% of the patients had had achieved a complete remission and 76% had undetectable MRD.
Afterwards, patients continued the triple combination in a maintenance phase until they achieved a complete remission and undetectable MRD. And with this continued maintenance treatment, the rate of complete remissions significantly increased to 44% and the best undetectable MRD rate increased to 93%. So 25 of the 45 patients were able to stop maintenance treatment early due to these deep remissions. And after the cessation of treatment, these deep remissions continued to remain and the progression free survival so far with this updated analysis is 90% at 30 months. So it’s quite a nice result for this high risk cohort.
Also, when looking at the patients who had already received the prior targeted agents, they did simultaneously well. The undetectable MRD rate in these patients did not differ from the entire cohort.
With regards to safety, we did not see any new signals or cumulative toxicity with the continued maintenance treatment.
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