Clinical trialPhase 3Lymphoma

Addition of autologous stem-cell transplantation to an ibrutinib-containing first-line treatment in patients aged 18-65 years with mantle cell lymphoma (TRIANGLE): 4·5-year follow-up of a three-arm, randomised, open-label, phase 3 superiority trial of the European MCL Network

Lancet · 2026870 patients (arm A: 288, arm A+I: 292, arm I: 290)

Dreyling M, Doorduijn J, Giné E, et al. Lancet. 2026. 407:1953-1967

Study type: Clinical trial
Study name: TRIANGLE
Phase: Phase 3
Design: Three-arm randomised (1:1:1), open-label, superiority trial at 165 centres in 13 European countries and Israel; median follow-up 54.9 months
Sample size: 870 patients (arm A: 288, arm A+I: 292, arm I: 290)
Source: Lancet · 2026
Trial registration: NCT02858258

In plain words

In mantle cell lymphoma, younger patients have traditionally had a transplant of their own stem cells (autologous transplant) after intensive chemotherapy. This new report of the TRIANGLE study, after about four and a half years of follow-up, showed that patients who took ibrutinib tablets with chemotherapy and then for two years, whether or not they had a transplant, had both better disease control and longer survival than with the old approach (chemotherapy and transplant without ibrutinib). Adding a transplant to treatment that includes ibrutinib gave no extra benefit but caused more side effects such as infections and low blood counts. This means many younger patients may be able to be treated without a transplant; talk this decision over with your doctor.

Key results

82% vs 81%

4-year FFS: A+I vs I

Superiority of A+I not shown; HR 0.86 (one-sided 98.33% CI 0.00 to 1.27); one-sided p = 0.21

82% vs 70%

4-year FFS: A+I vs A

HR 0.63 (one-sided 98.33% CI 0.00 to 0.89); one-sided p = 0.0026

70% vs 81%

4-year FFS: A vs I

Superiority of arm A not shown; HR 1.45; one-sided p = 0.99

88% vs 81%

4-year overall survival: A+I vs A

HR 0.59 (95% CI 0.38 to 0.92); p = 0.0036

90% vs 81%

4-year overall survival: I vs A

HR 0.57 (95% CI 0.36 to 0.90); p = 0.0019

Drugs in this study:Cisplatin (Platinol)Cyclophosphamide (Endoxan)Doxorubicin (Adriamycin)Ibrutinib (Imbruvica)Oxaliplatin (Eloxatin)Rituximab (Rituxan/MabThera)

Dose and schedule cards

Ibrutinib + immunochemotherapy (TRIANGLE trial)

Previously untreated stage II–IV mantle cell lymphoma, age 18 to 65 years, eligible for autologous transplantationOn the page “Lymphoma” · Treatment regimens and dosing: mantle cell lymphoma

Previously untreated stage II–IV mantle cell lymphoma, age 18 to 65 years, eligible for autologous transplantation

Drug	Dose	Route	Schedule
R-CHOP (alternating with R-DHAP)
Rituximab	375 mg/m²	IV	Day 0 or 1
Cyclophosphamide / doxorubicin	750 / 50 mg/m²	IV	Day 1
Vincristine	1.4 mg/m² (maximum 2 mg)	IV	Day 1
Prednisone	100 mg	Oral	Days 1–5
Ibrutinib	560 mg daily	Oral	Days 1–19
R-DHAP or R-DHAOx
Rituximab	375 mg/m²	IV	Day 0 or 1
Dexamethasone	40 mg	IV or oral	Days 1–4
Cytarabine	2 g/m² over 3 hours, twice, 12 hours apart	IV	Day 2
Cisplatin (or oxaliplatin 130 mg/m² in R-DHAOx)	100 mg/m² over 24 hours	IV	Day 1
Maintenance
Ibrutinib	560 mg daily	Oral	Continuously for 2 years

Cycle length: Every 21 days (6 alternating cycles)
Duration: 6 cycles, then with or without autologous transplantation, and 2 years of ibrutinib maintenance; rituximab maintenance was permitted according to national guidelines

Doses from the TRIANGLE abstract (4.5-year follow-up). Adding transplantation to the ibrutinib-containing regimen increased grade 3–5 haematologic toxicity and infections during maintenance.

On the page “Lymphoma” · Treatment regimens and dosing: mantle cell lymphoma

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Arm A (control): R-CHOP/R-DHAP + ASCT

Six alternating 21-day cycles of R-CHOP (rituximab 375 mg/m² IV day 0 or 1, cyclophosphamide 750 mg/m² day 1, doxorubicin 50 mg/m² day 1, vincristine 1.4 mg/m² day 1 [maximum 2 mg] and prednisone 100 mg orally days 1 to 5) and R-DHAP or R-DHAOx (rituximab 375 mg/m² IV day 0 or 1, dexamethasone 40 mg IV or orally days 1 to 4, high-dose cytarabine 2 × 2 g/m² IV over 3 hours every 12 hours on day 2, plus cisplatin 100 mg/m² IV over 24 hours day 1 [R-DHAP] or oxaliplatin 130 mg/m² IV day 1 [R-DHAOx]), followed by autologous transplantation.

2Arm A+I: same regimen + ibrutinib + ASCT

The arm A regimen plus ibrutinib 560 mg orally daily on days 1 to 19 of the R-CHOP cycles and as 2-year maintenance after autologous transplantation.

3Arm I: same regimen + ibrutinib without ASCT

Ibrutinib in the same way as arm A+I (in induction and 2-year maintenance), but without autologous transplantation. In all arms, rituximab maintenance was allowed according to national guidelines.

Source of the regimen details: Abstract of the paper on PubMed (Lancet 2026), which gives the doses in full

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients aged 18 to 65 years with previously untreated stage 2 to 4 mantle cell lymphoma (MCL) who were eligible for autologous stem-cell transplantation (ASCT).

Endpoints

Primary endpoint: failure-free survival (FFS), tested with three pairwise one-sided log-rank tests.

Other endpoints: overall survival and safety.

Safety and side effects

During maintenance or follow-up, the most common grade 3 to 5 adverse events were haematological: 127 of 234 patients (54%) in arm A+I, 74 of 269 (28%) in arm I and 56 of 240 (23%) in arm A; and infections: 80 of 234 (34%) in arm A+I, 71 of 269 (26%) in arm I and 37 of 240 (15%) in arm A. Infections were the most common fatal adverse event in this period: four patients (2%) in arm A+I and five patients (2%) in arm I.

Clinical significance and place in guidelines

With longer follow-up, this analysis showed that adding ASCT to an ibrutinib-containing regimen gives no additional benefit and increases toxicity, and for the first time reported improved overall survival with both ibrutinib-containing arms versus the previous standard treatment. The authors propose ibrutinib + R-CHOP/R-DHAP induction followed by 2-year ibrutinib maintenance without transplantation as the new standard for younger patients with MCL.

Limitations

The study was open-label. Only transplant-eligible patients aged 18 to 65 years were enrolled. Rituximab maintenance was allowed according to national guidelines and may have differed between centres. Overall survival comparisons are secondary endpoints.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.