ASH 2020 | SEQUOIA: zanubrutinib-based treatment for CLL with del(17p)
Constantine Tam, MBBS (Hons), MD, FRACP, FRCPA, The Peter MacCallum Cancer Centre, Melbourne, Australia, outlines results from the Phase III SEQUOIA trial (NCT03336333), which investigated the efficacy and safety of the next-generation BTK inhibitor zanubrutinib in patients with high-risk chronic lymphocytic leukemia (CLL). Arm C of the trial studied a non-randomized cohort of del(17p)-positive patients treated with zanubrutinib. Updated analyses from an 18-month follow-up showed encouraging results in line with previous reports, with high rates of durable responses and an estimated 18-month progression-free survival of nearly 90%. Arm D, investigating combined zanubrutinib and venetoclax, was designed based on early clinical benefits and tolerability seen in arm C. Del(17p) patients are being recruited currently and serial measurable residual disease monitoring will be used to determine treatment discontinuation. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.
Transcript (edited for clarity)
SEQUOIA study is a study testing the next-generation BTK inhibitor zanubrutinib in CLL and the SEQUOIA actually has four arms. So the initial two arms are Arm A and Arm B, which are randomized arms comparing bendamustine-rituximab against zanubrutinib as frontline treatment of CLL. But clearly, these patients with 17p deletion identified during screening are not really a good patient for Arm A or Arm B...
SEQUOIA study is a study testing the next-generation BTK inhibitor zanubrutinib in CLL and the SEQUOIA actually has four arms. So the initial two arms are Arm A and Arm B, which are randomized arms comparing bendamustine-rituximab against zanubrutinib as frontline treatment of CLL. But clearly, these patients with 17p deletion identified during screening are not really a good patient for Arm A or Arm B. So a non-randomized Arm C was set up to accept other patients who have 17p deletion to receive zanubrutinib as a single agent without randomization.
As it turned out, in the end, we accrued 109 patients frontline with 17p CLL. And this is one of the largest experience of 17p CLL frontline treatment in any trial out there. And all of these patients were treated with zanubrutinib single agent, and what we showed was that the toxicity was tolerable. In fact, it’s similar to zanubrutinib in other diseases, i.e., similar to ibrutinib but with lower incidence of atrial fibrillation and bleeding, and the overall response rate was actually very encouraging at 94.5%. In this meeting we updated the progression-free survival, which, at 18 months, is 91%.
So it shows that in this very adverse group of patients with 17p deletion CLL, and in a large group of patients, 109, treated uniformly with zanubrutinib, that we had good response rates and good progression-free survival rates at 18 months. And that led to the establishment of the Arm D. So once the Arm C was fully recruited, the question then came about, can we improve upon those results by treating additional patients using the combination this time of zanubrutinib and venetoclax? And that is what the Arm D is about.
So now, patients who have 17p deletion enrolled in the SEQUOIA Study, are now all are enrolled into the non-randomized Arm D. And this is a trial in progress. We have patients who have successfully dose-escalated under the combination of zanubrutinib and venetoclax and we’re hoping to enroll a total of 50 patients in the end to give us one of the largest experience of this doublet in patients with 17p deletion. So there is a trial in progress for the Arm D arm.
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Disclosures
Prof. Constantine Tam, MBBS (Hons), MD, FRACP, FRCPA, has received honoraria from Beigene, Janssen and AbbVie.
