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NEW ORLEANS -- In patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), progression-free survival (PFS) was significantly longer among those who received zanubrutinib (Brukinsa) compared with ibrutinib (Imbruvica), results from the showed.

At a median follow-up of 29.6 months, there were 87 occurrences of disease progression or death with the second-generation Bruton's tyrosine kinase (BTK) inhibitor compared with 118 occurrences with ibrutinib (HR 0.65, 95% CI 0.49-0.86, P=0.002), with 2-year investigator-assessed PFS rates of 78.4% and 65.9%, respectively, reported Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute in Boston.

In the highest-risk group -- those with 17p deletion, a TP53 mutation, or both -- patients who received zanubrutinib also had longer PFS than those who received ibrutinib as assessed both by the investigators (24 and 36 occurrences of disease progression or death; HR 0.53, 95% CI 0.31-0.88) and by the independent review committee (23 and 34 events; HR 0.52, 95% CI 0.30-0.88).

This study was presented at the 2022 American Society of Hematology (ASH) annual meeting and published simultaneously in the .

"The investigator-determined results were extremely concordant," Brown said during a press briefing at ASH. "ALPINE is the first study to demonstrate PFS superiority in a head-to-head comparison of BTK inhibitors in patients with relapsed/refractory CLL/SLL. This is a practice-changing trial."

The overall response rate as assessed by independent review was also higher with zanubrutinib compared with ibrutinib (86.2% vs 75.7%).

While zanubrutinib is not yet approved for CLL/SLL -- the FDA has set a Prescription Drug User Fee Act goal date of Jan. 20, 2023 for the supplementary new drug application -- "we're hoping that is going to happen imminently," she noted. "The data have been accumulating over the last year. We had the frontline randomized trial with significant benefit for zanubrutinib, the early report of ALPINE was encouraging, and now this more mature data at 30 months follow-up with ALPINE is definitive."

When asked whether she sees a role for ibrutinib in CLL patients going forward, Brown said she was "not aware of a patient population in which I would select ibrutinib as compared to zanubrutinib, and that is actually reflected in in which zanubrutinib is now listed as preferred, and ibrutinib as another recommended regimen."

The open-label ALPINE trial included 652 patients and was conducted at 113 sites across 15 countries from November 2018 to December 2020. Brown and team randomized patients with relapsed or refractory CLL or SLL who had received at least one prior line of therapy 1:1 to the zanubrutinib and ibrutinib arms. Median age was 67 years, 81% were white, and 14% were Asian.

Of the patients, 45% entered the trial with bulky disease, and 23% had a chromosome 17p deletion, TP53 mutation, or both. The median number of previous lines of therapy was one, and 8% of patients had received more than three lines of therapy; 80% of those in the zanubrutinib group and 76% of those in the ibrutinib group had previously received chemoimmunotherapy.

Median treatment duration was 28.4 months with zanubrutinib versus 24.3 months with ibrutinib. At the time of data cutoff, treatment was ongoing in 73% of patients in the zanubrutinib arm and 58% in the ibrutinib arm.

There were fewer serious adverse events (AEs) with zanubrutinib (42.0% vs 50.0%), and fewer AEs leading to dose reductions (12.3% vs 17.0%), dose interruptions (50.0% vs 56.8%), and treatment discontinuations (15.4% vs 22.2%).

A lower incidence of cardiac disorders was also reported in the zanubrutinib group (21.3%) versus the ibrutinib group (29.6%), and there was just one cardiac AE leading to treatment discontinuation with zanubrutinib compared with 14 with ibrutinib.

Importantly, the incidence of atrial fibrillation or flutter of any grade was lower in the zanubrutinib group than in the ibrutinib group (5.2% vs 13.3%), Brown noted.

Fewer deaths were reported with zanubrutinib than ibrutinib -- 14.7% vs 18.5% (HR 0.76, 95% CI 0.51-1.11) -- though this was not statistically significant.

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