SYMPATICO
SYMPATICO showed that adding the BCL2 blocker venetoclax to ibrutinib for people whose mantle cell lymphoma had returned kept the disease under control for about ten months longer than ibrutinib alone, and the combination also produced complete responses in most untreated patients with the hard-to-treat TP53 mutation.
Overview
SYMPATICO was a phase 3 trial by Pharmacyclics and Janssen in 366 patients. After a safety run-in that monitored tumour lysis syndrome, patients with relapsed or refractory mantle cell lymphoma were randomised double-blind to ibrutinib 560 mg daily with venetoclax (ramped to 400 mg) for two years or with placebo; a separate open-label arm gave the combination to treatment-naive patients with TP53-mutated disease. The primary endpoint of the randomised phase was investigator-assessed progression-free survival.
In the registry results, at a median time on study of 61.3 months, median progression-free survival was 31.9 months with ibrutinib-venetoclax against 22.1 months with ibrutinib-placebo (hazard ratio 0.629), and the complete response rate in the treatment-naive TP53-mutated arm was 69.2 percent. One tumour lysis syndrome event occurred in the run-in among patients at increased risk. The corpus's mantle cell lymphoma page lists a BTK inhibitor with or without venetoclax on this trial.
- Median 31.9 vs 22.1 months with Ibrutinib + venetoclax compared with Ibrutinib + placebo; about 9.8 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 37 percent lower chance of the event at any given time (hazard ratio 0.629, likely range 0.465 to 0.85).
- 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.
- 69.2 out of 100 people had their tumour shrink with Ibrutinib + venetoclax, open label.
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- Increased tumour lysis risk at baseline: 1 participants; Low tumour lysis risk at baseline: 0 participants.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- These results apply to the people the trial enrolled: Relapsed or refractory mantle cell lymphoma after one to five prior lines: ibrutinib with venetoclax or with placebo (double-blind), after a safety run-in for tumour lysis syndrome, plus an open-label treatment-naive arm of the combination in patients with TP53 mutation. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (TP53); 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.
366 enrolled.
95% CI 22.8 to 54.5; median time on study 61.3 months · 95% CI 16.5 to 29.5
Source95% CI 57.8 to 79.2; median time on study 40.5 months
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival, randomised phase (registry results)primary | Ibrutinib + venetoclax | - | 31.9 months | 0.629 (0.465 to 0.85) | 0.0024 | link |
| Ibrutinib + placebo | - | 22.1 months | ||||
| Complete response rate, treatment-naive TP53-mutated arm (registry results)primary | Ibrutinib + venetoclax, open label | - | 69.2% | - | - | link |
| Tumour lysis syndrome events in the safety run-in (registry results) | Increased tumour lysis risk at baseline | 15 | 1 participants | - | - | link |
| Low tumour lysis risk at baseline | 6 | 0 participants |
Similar pages
not linked directly; found by shared links- TrialCLL12
Shares Ibrutinib, Johnson & Johnson, Small-molecule kinase inhibitors and the tag soc-trials.
- TrialTRIANGLE
Shares Ibrutinib, Mantle cell lymphoma, Non-Hodgkin lymphoma (all types), Small-molecule kinase inhibitors and the tag soc-trials.
- TrialDRAMMATIC
Shares Johnson & Johnson and the tag soc-trials.
- TrialIMpactMF
Shares Small-molecule kinase inhibitors and the tag soc-trials.
- TrialCOMFORT-I
Shares Small-molecule kinase inhibitors and the tag soc-trials.
- TrialCOMFORT-II
Shares Small-molecule kinase inhibitors and the tag soc-trials.
- TrialFoRT
Shares Non-Hodgkin lymphoma (all types) and the tag soc-trials.
- TrialA Study to Customize Ibrutinib Treatment Regimens for Participants With Previously Untreated Chronic Lymphocytic Leukemia
Shares Ibrutinib, AbbVie (incl. ImmunoGen, Capstan), Johnson & Johnson, Venetoclax.