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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.
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.
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 |
Shares Ibrutinib, Johnson & Johnson, Small-molecule kinase inhibitors and the tag soc-trials.
Shares Ibrutinib, Mantle cell lymphoma, Non-Hodgkin lymphoma (all types), Small-molecule kinase inhibitors and the tag soc-trials.
Shares Johnson & Johnson and the tag soc-trials.
Shares Ibrutinib, AbbVie (incl. ImmunoGen, Capstan), Johnson & Johnson, Venetoclax.
Shares Small-molecule kinase inhibitors and the tag soc-trials.
Shares Small-molecule kinase inhibitors and the tag soc-trials.
Shares Small-molecule kinase inhibitors and the tag soc-trials.
Shares Small-molecule kinase inhibitors and the tag soc-trials.