ALPINE and SEQUIOA Demonstrate Effectiveness of Zanubrutinib in CLL/SLL

Cyrus M. Khan, MD, a hematologist at the Allegheny Health Network Cancer Institute, discusses the study results that demonstrated the superiority of zanubrutinib (Brukinsa) over ibrutinib (Imbruvica) and bendamustine (Bendeka) and rituximab (Rituxan) for both untreated and relapsed/refractory patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

The studies that demonstrated the efficacy of the next generation Bruton’s tyrosine kinase (BTK) inhibitor included the phase 3 ALPINE study (NCT03734016) and phase 3 SEQUOIA study (NCT03336333). The ALPINE study was a global phase 3 randomized study that compared zanubrutinib to ibrutinib in about 600 patients with relapsed/refractory CLL or SLL, whereas the SEQUOIA study looked at the use zanubrutinib in the frontline setting for patients with CLL or SLL.

Both studies showed that the use of zanubrutinib produced superior results for these patients. In the case of the ALPINE study the 24-month PFS rate was 79.5% with the next generation BTK inhibitor compared with 67.3% for patients on ibrutinib. Moreover, the study reached its primary end point of objective response rate (ORR) of 86.2% with zanubrutinib vs 75.7% on ibrutinib (P = .0007). The SEQUIOA study further showed the potential of the BTK inhibitor with a significant increase to PFS compared with bendamustine and rituximab (HR, 0.42; 95% CI: 0.28-0.63, P < .0001).

Khan discusses how these results, and the adverse event (AE) data, have impacted physician decisions for this patient population.

Transcript:

0:08 | In the Alpine study compared zanubrutinib in relapsed/refractory CLL patients with Ibrutinib in the relapsed/refractory second line setting.... If you follow those patients over a period of time, and this was a superiority trial, so it set off to show that z zanubrutinib is superior to ibrutinib, and it showed that the PFS was better. Of course, we don't have data yet about OS since that takes many years, but it also showed that in some respects, the AE profile was cleaner as well, particularly in cardiovascular areas, with lesser fibrillation/flutter [rates] and in overall cardiac disease as well. The key point here is that, in this day and age, if we have to start a patient on a BTK inhibitor for CLL/SLL, [we're] probably using a second generation BTK inhibitor like zanubrutinib, or acalabrutinib, is the better choice rather than ibrutinib.

1:06 | As far as SEQUOIA is concerned, that was a frontline study comparing zanubrutinib to patients with bendamustine rituximab in a frontline setting. So, 6 months of BR vs continuous zanubrutinib, and that also showed at 2 years, at least, that BTK inhibition was better. The PFS, I believe, was almost 84% or so in zanubrutinib and it was also almost the same for patients with 17P-deletion, which is a high-risk disease, [which] certainly beats out frontline chemotherapy as well.