Johnson & Johnson Seeks EMA Approval for Ibrutinib Plus R-CHOP in Frontline MCL

A type II variation application has been submitted by Johnson & Johnson to the European Medicines Agency (EMA) seeking approval for an indication extension of ibrutinib (Imbruvica) in combination with rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) in autologous stem cell transplant (ASCT)–eligible adult patients with treatment-naive mantle cell lymphoma (MCL).1 The proposed indication is supported by results from the phase 3 TRIANGLE trial (NCT02858258).

Findings from TRIANGLE, which was conducted by the European MCL Network, presented during the 2024 ASH Annual Meeting and Exposition demonstrated that patients who received R-CHOP alone (n = 288) achieved a 4-year failure-free survival (FFS) rate of 70% compared with 82% among patients who were treated with ibrutinib in combination with R-CHOP (n = 292).2 At a median follow-up of 55 months, the median FFS was not reached in either arm (HR, 0.64; P = .0026). The 4-year overall survival (OS) rates were 81% and 88%, respectively (HR, 0.587; P = .0036).

“MCL remains an incurable and challenging disease to treat, particularly in younger patients in need of durable frontline options,” Edmond Chan, MBChB, MD (Res), EMEA Therapeutic Area Lead Hematology, Johnson & Johnson Innovative Medicine, stated in a news release.1 “The TRIANGLE study demonstrates ibrutinib’s potential to replace or complement a transplant-based regimen, offering eligible patients a more effective path to long-term remission and representing the first major step forward in frontline MCL treatment in years.”

TRIANGLE enrolled previously untreated patients with stage II to IV MCL who were younger than 66 years of age.2 In order to be eligible for the study, patients needed to be suitable for high-dose cytarabine and ASCT as well as have an ECOG performance status of 2 or less.

Patients (n = 870) were randomly assigned 1:1:1 to receive 3 cycles of R-CHOP followed by ASCT and observation; R-CHOP plus ibrutinib followed by ASCT, 2 years of ibrutinib maintenance, and observation; or R-CHOP plus ibrutinib followed by 2 years of ibrutinib maintenance, and observation. The primary end point was FFS. Secondary end points included response rate, OS, and safety.

The median age in the overall population was 57 years (range, 27-68) and most patients were male (76%). Patients had Ann Arbor stage I (n = 1), II (4%), III (8%), or IV (87%) disease. Patients had either Mantle Cell Lymphoma International Prognostic Index (MIPI) low (58%), intermediate (27%), or high (15%) disease.

Additional findings from TRIANGLE showed that the MIPI-adjusted HR favored ibrutinib plus R-CHOP over R-CHOP alone in patients with blastoid cytology (HR, 0.57; 95% CI, 0.0-1.32), p53 low disease (HR, 0.85; 95% CI, 0.0-1.44), and p53 high disease (HR, 0.68; 95% CI, 0.0-1.80).

“At Johnson & Johnson, we are committed to investing in innovation that transforms clinical outcomes for those living with complex blood cancers, including MCL,” Jessica Vermeulen, vice president, Oncology Late Development, Johnson & Johnson Innovative Medicine, added in the news release.1 “Today’s submission to the EMA could represent a pivotal step in moving beyond transplant as the frontline standard of care for younger patients with MCL.”

References

1. Johnson & Johnson submits application to the European Medicines Agency seeking approval of a new indication for IMBRUVICA (ibrutinib) in adult patients with previously untreated mantle cell lymphoma (MCL) who are eligible for autologous stem cell transplant. News release. Johnson & Johnson. December 18, 2024. Accessed December 18, 2024. https://www.globenewswire.com/news-release/2024/12/18/2998796/0/en/Johnson-Johnson-submits-application-to-the-European-Medicines-Agency-seeking-approval-of-a-new-indication-for-IMBRUVICA-ibrutinib-in-adult-patients-with-previously-untreated-mantle.html
2. Dreyling M, Doorduijn JK, Gine E, et al. Role of autologous stem cell transplantation in the context of ibrutinib-containing first-line treatment in younger patients with mantle cell lymphoma: results from the randomized triangle trial by the European MCL Network. Blood. 2024;144(suppl 1):240. doi:10.1182/blood-2024-200735