Background
Autologous stem-cell transplant (ASCT) was the standard consolidation in younger MCL patients. TRIANGLE tested whether adding ibrutinib to induction/maintenance permits omission of ASCT, and whether ibrutinib + ASCT is superior to ASCT alone, in transplant-eligible MCL aged ≤65.
Interventions and follow up
Arm A (control): R-CHOP/R-DHAP induction + ASCT, then observation
Arm A+I: Ibrutinib added to induction (I+R-CHOP/R-DHAP) + ASCT + ibrutinib maintenance x2 years
Arm I: Ibrutinib added to induction + ibrutinib maintenance x2 years (no ASCT)
Population: N=870, untreated MCL, transplant-eligible
Primary endpoint: failure-free survival (FFS)
Median follow-up: 31 months
Arm A+I: Ibrutinib added to induction (I+R-CHOP/R-DHAP) + ASCT + ibrutinib maintenance x2 years
Arm I: Ibrutinib added to induction + ibrutinib maintenance x2 years (no ASCT)
Population: N=870, untreated MCL, transplant-eligible
Primary endpoint: failure-free survival (FFS)
Median follow-up: 31 months
Results
3-yr FFS, Arm I vs Arm A: 86% vs 72% (HR 0.52); non-inferiority criterion met
3-yr FFS, Arm A+I vs Arm A: 88% vs 72% (HR 0.49, P<.001), superiority shown
Arm A+I vs Arm I: no clear benefit of adding ASCT to ibrutinib (could not establish superiority)
OS: immature, trend favoring ibrutinib-containing arms
3-yr FFS, Arm A+I vs Arm A: 88% vs 72% (HR 0.49, P<.001), superiority shown
Arm A+I vs Arm I: no clear benefit of adding ASCT to ibrutinib (could not establish superiority)
OS: immature, trend favoring ibrutinib-containing arms
Adverse events
Hematologic: Grade 3-4 neutropenia and thrombocytopenia highest in Arm A+I (ibrutinib during/after ASCT)
Cardiac: atrial fibrillation and hypertension more frequent in ibrutinib arms
Infections: grade 3-5 infections increased in Arm A+I
Other: Arm I (no ASCT) had the most favorable toxicity profile; treatment-related deaths ~1% across arms
Cardiac: atrial fibrillation and hypertension more frequent in ibrutinib arms
Infections: grade 3-5 infections increased in Arm A+I
Other: Arm I (no ASCT) had the most favorable toxicity profile; treatment-related deaths ~1% across arms
Conclusions
Ibrutinib-containing induction plus maintenance was superior to ASCT alone, and ASCT added no clear benefit when ibrutinib was given. Practice-changing: ASCT can be safely omitted in younger MCL receiving ibrutinib-based therapy.
Key Limitations
Median follow-up still short (31 months) for a disease with long natural history; OS immature; three-arm design complicates direct conclusions about ASCT; ibrutinib used despite later MCL withdrawal in some markets; TP53-mutated patients remain high-risk; added toxicity when ASCT and ibrutinib combined.
Clinical Context
TRIANGLE challenges the long-standing ASCT consolidation paradigm in younger MCL, supporting a chemoimmunotherapy + BTK-inhibitor strategy without transplant. ESMO guidance now incorporates BTK-inhibitor-based induction; given ibrutinib's MCL withdrawal, second-generation BTK inhibitors are being substituted in practice and ongoing trials.