Background
Phase II, single-arm study. 131 patients with newly diagnosed mantle cell lymphoma (MCL) aged ≤65, transplant-eligible. Tested an ibrutinib "window" induction followed by ibrutinib + chemoimmunotherapy, aiming to reduce disease burden and test BTK inhibitor activity before cytotoxic exposure.
Interventions and follow up
Regimen: Ibrutinib 560 mg PO daily × 12 weeks (window) then ibrutinib + R-CHOP alternating with R-HCVAD for up to 8 chemoimmunotherapy cycles, without ASCT consolidation; in newly diagnosed MCL aged ≤65
Primary endpoint: Complete response rate after the ibrutinib window plus chemoimmunotherapy
Median follow-up: 47.3 months
Primary endpoint: Complete response rate after the ibrutinib window plus chemoimmunotherapy
Median follow-up: 47.3 months
Results
CR rate (overall): 89% (95% CI 82–94%)
ORR after ibrutinib window alone: 67% (CR 12%)
3-year PFS: 86%
3-year OS: 94%
MRD negativity (peripheral blood): 87%
ORR after ibrutinib window alone: 67% (CR 12%)
3-year PFS: 86%
3-year OS: 94%
MRD negativity (peripheral blood): 87%
Adverse events
Hematologic/infectious: Grade ≥3 AEs 75%; grade ≥3 neutropenia 56%; grade ≥3 infections 15%.
Cardiac/bleeding: Atrial fibrillation any grade 5%; bleeding any grade 28%; three treatment-related deaths (1 cardiac, 1 sepsis, 1 multi-organ failure).
Cardiac/bleeding: Atrial fibrillation any grade 5%; bleeding any grade 28%; three treatment-related deaths (1 cardiac, 1 sepsis, 1 multi-organ failure).
Conclusions
An ibrutinib window plus chemoimmunotherapy without ASCT achieved exceptional CR rates (89%) and 3-year PFS (86%) in transplant-eligible MCL, establishing this as a highly active chemotherapy-sparing approach and supporting further evaluation.
Key Limitations
Single-arm, single-institution phase II without a randomized comparator. Did not include ASCT, so it cannot be directly compared with transplant-based induction. Three treatment-related deaths and substantial hematologic toxicity. Longer follow-up is needed to establish durability, and ibrutinib is no longer routinely available in some markets following voluntary MCL withdrawals.
Clinical Context
WINDOW-1 supports incorporating BTK inhibitors into frontline MCL induction, consistent with the broader move toward chemotherapy-sparing strategies. The randomized TRIANGLE trial separately established a frontline role for ibrutinib added to induction. ASCO/ESMO guidance increasingly favors BTK inhibitor-containing induction; the optimal regimen and the continued need for ASCT remain active questions.