BRUIN CLL-321
The randomised trial that confirmed pirtobrutinib works after other BTK inhibitors fail, leading to full approval in December 2025.
Median PFS 11.2 vs 8.7 months (HR 0.58), with longer time to next treatment; OS not different (crossover). ASH 2024; JCO 2025. Converted the accelerated approval to traditional approval on 3 December 2025 and broadened the label to any prior covalent BTKi.
Setting
Relapsed/refractory CLL/SLL after a covalent BTK inhibitor: pirtobrutinib vs investigator's choice (idelalisib-rituximab or bendamustine-rituximab)
Phase
Phase 3
Sponsor
Eli Lilly / Loxo
Registry
Headline result
PFS 11.2 vs 8.7 months; HR 0.58.
Reported
2024
Enrolled
238
Replication
BRUIN phase 1/2 (n>300 CLL) showed ORR ~82% after covalent BTKi; frontline randomised trials (CLL-313, CLL-314) pending.
In plain words
What these results mean for people, not percentages
Progression-free survival (median)primarysurrogate endpoint
- Median 11.2 vs 8.7 months with Pirtobrutinib compared with Idelalisib-rituximab or bendamustine-rituximab; about 2.5 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 42 percent lower chance of the event at any given time (hazard ratio 0.58).
- 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: Relapsed/refractory CLL/SLL after a covalent BTK inhibitor: pirtobrutinib vs investigator's choice (idelalisib-rituximab or bendamustine-rituximab). People in a different situation may not see the same effect.
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.
238 participants enrolled.
Progression-free survival (median)primary
HR 0.58
Pirtobrutinib
11.2 mo
Idelalisib-rituximab or bendamustine-rituximab
8.7 mo
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (median)primary | Pirtobrutinib | 119 | 11.2 months | 0.58 | — | link |
| Idelalisib-rituximab or bendamustine-rituximab | 119 | 8.7 months |
Replication
BRUIN phase 1/2 (n>300 CLL) showed ORR ~82% after covalent BTKi; frontline randomised trials (CLL-313, CLL-314) pending.