TITLE

Real-world implementation of the TRIANGLE regimen (without ASCT) in newly diagnosed mantle cell lymphoma: A multicenter analysis of effectiveness and safety

AUTHORS

Bedoya T¹, Quintela D¹, Villalobos MT², Kelleher N³, Rodriguez M⁴, Piernas S⁵, Ferrero A⁶, Sancho JM¹

AFFILIATIONS

1. Clinical hematology service, Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.

2. Clinical hematology service, Hospital Mutua de Terrassa, Terrassa, Barcelona, Spain.

3. Clinical hematology service, Institut Català d'Oncologia, Hospital Josep Trueta, Girona, Spain.

4. Clinical hematology service, Institut Català d'Oncologia, Hospital Universitari Verge de la Cinta, Tortosa, Tarragona, Spain.

5. Clinical hematology service, Hospital Universitario Arnau de Vilanova, Lleida, Spain.

6. Clinical hematology service, Hospital Parc Taulí, Sabadell, Barcelona, Spain.

INTRODUCTION & BACKGROUND

The landmark Phase III TRIANGLE trial redefined the frontline treatment of transplant-eligible mantle cell lymphoma (MCL) by demonstrating that adding ibrutinib to R-CHOP/R-DHAP induction and maintenance significantly improves outcomes. However, the translation of these clinical trial results into routine daily clinical practice requires active real-world validation.

AIM & OBJECTIVES

We aimed to evaluate the effectiveness and safety of the TRIANGLE regimen in a real-world multicenter cohort of patients with newly diagnosed mantle cell lymphoma (MCL) outside of clinical trials.

METHODS

• Study Design: Retrospective, multicenter study across seven Spanish centers.

• Cohort Size: 27 patients with newly diagnosed MCL treated according to the no-ASCT TRIANGLE schema branch between 2024 and 2025.

• Analyzed Variables: Baseline clinic-biological variables, response rates evaluated according to Lugano criteria, and safety profile via CTCAE grade 3 adverse events (AEs).

RESULTS

Response Rates & Feasibility

• Median Follow-up: 12.2 months (range, 2.1-25.5) with 23 patients evaluable post-induction.

• Post-induction Response: 100% Overall Response Rate (ORR), with 87% Complete Response rate (CR; n=20), and 13% Partial Response rate (PR; n=3).

• Treatment Transition: 0% of patients proceeded to autologous stem cell transplantation (ASCT). 100% transitioned directly to ibrutinib-based maintenance (78% ibrutinib-rituximab).

• Long-term Efficacy: 100% overall survival to date; 22/23 patients (95%) maintain CR. Only 1 relapse occurred (high-risk features: blastoid variant, TP53 mutation, Ki-67 > 30%).

Safety Profile (Bimodal Toxicity)

• Induction Phase (n=27): Ibrutinib delays/interruptions occurred in 14% of patients (primarily grade $\ge$3 neutropenia (11.1%) and bleeding (3.7%)). 0% definitive discontinuations. Most frequent AEs: infections (29%) and grade $\ge$3 neutropenia (25%).

• Maintenance Phase (n=23): 17.4% required dose reductions (to 420 mg) and 17.4% required temporary interruptions (due to gastrointestinal toxicity, bleeding, or infections). Only 1 patient (4.3%) discontinued treatment definitively (due to disease progression).

• Maintenance AEs: Shift towards chronic toxicity: most frequent were hypertension (13%), bleeding (13%), and infections (13%).

CONCLUSIONS

Our data suggest that the TRIANGLE regimen is highly effective and feasible in real-world clinical practice, showing a safety profile consistent with clinical trials. The high complete response rate and limited toxicity strongly support its frontline use. Importantly, the zero-rate of ASCT in this series reflects a shifting paradigm toward ibrutinib-based consolidation in the "real world" setting.

TABLES (For text box insertion if required)

Table 1: Baseline Characteristics

• Age in years, median (range): 60 (43-74)

• Male sex, n (%): 20 (74.1%)

• ECOG Performance Status 0-1 / $\ge$2: 26 (96.3%) / 1 (3.7%)

• Advanced Ann Arbor Stage (III-IV): 25 (92.6%)

• MIPI (Low / Intermediate / High Risk): 6 (22.2%) / 11 (40.7%) / 10 (37.0%)

• Ki-67 (<30% / $\ge$30% / Not available): 15 (55.6%) / 10 (37.0%) / 2 (7.4%)

• Histology (Classical / Blastoid / Other Variant): 19 (70.4%) / 3 (11.1%) / 5 (18.5%)

• TP53 Status (Negative WT / Positive): 19 (70.4%) / 3 (11.1%)

Table 2: Adverse Event / Tolerability

• Infections: Induction 8 (29%) | Maintenance 3 (13%)

• Hematological (Neutropenia $\ge$3): Induction 7 (25%) | Maintenance 3 (13%)

• Hemorrhagic: Induction 1 (3.7%) | Maintenance 3 (13%)

• Cardiovascular (AF/HTN): Induction 1 (3.7%) | Maintenance 3 (13%)

• Gastrointestinal: Induction 0 (0%) | Maintenance 2 (8.6%)

• Delay/Temporary interruption: Induction 4 (14%) | Maintenance 4 (17.4%)

• Dose reduction (to 420 mg): Induction 0 (0%) | Maintenance 4 (17.4%)

• Definitive discontinuation (due to AE): Induction 0 (0%) | Maintenance 0 (0%)

ACKNOWLEDGEMENTS

We thank all participating patients, their families, and the medical and nursing staff across the six Spanish participating clinical centers for making this real-world analysis possible.

CONTACT INFORMATION

• Lead Presenting Author: Teresa Bedoya Palop

• Email: tbedoyap.germanstrias@gencat.cat

• Institution: Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain

REFERENCES

1. Dreyling M, et al. TRIANGLE ibrutinib added to induction and autologous stem-cell transplantation in mantle cell lymphoma. The Lancet, 2024.

2. Cheson BD, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol, 2014.