SEQUOIA
Zanubrutinib beat chemoimmunotherapy in untreated CLL and delivered a 72% five-year progression-free rate in the hardest genetic subgroup.
Cohort 1 (n=479): PFS HR 0.42 (95% CI 0.28-0.63) at primary analysis; 5-year follow-up maintains benefit. Arm C (del(17p), n=111): 5-year PFS 72.2%. Arm D (zanubrutinib + venetoclax): ORR 96-99%, uMRD ~60% at 24 months. Lancet Oncology 2022; JCO 2025. Basis of the January 2023 CLL approval.
Setting
Previously untreated CLL/SLL unsuitable for FCR: zanubrutinib vs bendamustine-rituximab (cohort 1); zanubrutinib in del(17p) (arm C); zanubrutinib + venetoclax (arm D)
Phase
Phase 3
Sponsor
BeOne (BeiGene)
Registry
Headline result
PFS HR 0.42 vs BR; 5-year PFS 72.2% in del(17p).
Reported
2022
Enrolled
590
Replication
ALPINE confirmed zanubrutinib's efficacy against ibrutinib in relapse; ELEVATE-TN shows the same class effect frontline.
In plain words
What these results mean for people, not percentages
Progression-free survival (cohort 1)primarysurrogate endpoint
- The treated group had about 58 percent lower chance of the event at any given time (hazard ratio 0.42).
- The absolute difference, how many more people out of 100 were helped, is not reported here.
Progression-free survival at 5 years, del(17p) (arm C)surrogate endpoint
- 72.2 out of 100 people alive without the cancer growing at 5 years with Zanubrutinib.
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
Be careful
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- These results apply to the people the trial enrolled: Previously untreated CLL/SLL unsuitable for FCR: zanubrutinib vs bendamustine-rituximab (cohort 1); zanubrutinib in del(17p) (arm C); zanubrutinib + venetoclax (arm D). People in a different situation may not see the same effect.
- The trial selected people by a biomarker (17p); the result should not be assumed for people whose cancer does not have it.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
590 participants enrolled.
Progression-free survival (cohort 1)primary
HR 0.42 (0.28–0.63) · p <0.0001
Numbers not yet public.
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (cohort 1)primary | Zanubrutinib | 241 | — | 0.42 (0.28–0.63) | <0.0001 | link |
| Bendamustine + rituximab | 238 | — | ||||
| Progression-free survival at 5 years, del(17p) (arm C) | Zanubrutinib | 111 | 72.2% | — | — | link |
Replication
ALPINE confirmed zanubrutinib's efficacy against ibrutinib in relapse; ELEVATE-TN shows the same class effect frontline.