EMA to Review Ibrutinib for Frontline Mantle Cell Lymphoma in Transplant-Eligible Patients
Key Insights
Johnson & Johnson seeks EMA approval for ibrutinib plus R-CHOP for untreated MCL patients eligible for autologous stem cell transplant.
The application is based on the Phase 3 TRIANGLE study, which showed improved efficacy with ibrutinib-based regimens.
TRIANGLE study investigated ibrutinib with immunochemotherapy, with and without transplant, compared to standard immunochemotherapy followed by transplant.
Janssen-Cilag International NV, a Johnson & Johnson company, has submitted a Type II variation application to the European Medicines Agency (EMA) seeking approval for IMBRUVICA® (ibrutinib) in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) for the treatment of adult patients with previously untreated mantle cell lymphoma (search) (MCL) who are eligible for autologous stem cell transplant. The submission is supported by data from the Phase 3 TRIANGLE study.
The TRIANGLE study, conducted by the European MCL Network, investigated 870 patients across three treatment arms: standard induction immunochemotherapy followed by transplant, induction immunochemotherapy plus ibrutinib followed by transplant and 2-year fixed-duration ibrutinib therapy, and induction immunochemotherapy plus ibrutinib without transplant, followed by 2-year fixed-duration ibrutinib therapy.
TRIANGLE Study Results
The TRIANGLE study demonstrated that both ibrutinib-based regimens, with and without transplant, delivered clinically meaningful improvement in efficacy compared to the current standard of care of induction immunochemotherapy followed by transplant. At the 2024 American Society of Hematology (ASH) Annual Meeting, Prof. Dr. Martin Dreyling presented prolonged efficacy and safety data from the TRIANGLE study.
According to findings from the TRIANGLE trial presented at the 2024 ASH Annual Meeting and Exposition, 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). 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).
Expert Commentary
"Mantle cell lymphoma (search) remains an incurable and challenging disease to treat, particularly in younger patients in need of durable frontline options," said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Haematology, Johnson & Johnson Innovative Medicine. "The TRIANGLE study demonstrates ibrutinib’s potential to replace or compliment a transplant-based regimen, offering eligible patients a more effective path to long term remission and representing the first major step forward in frontline mantle cell lymphoma treatment in years."
Jessica Vermeulen, Vice President, Oncology Late Development, Johnson & Johnson Innovative Medicine, stated, "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 mantle cell lymphoma (search)."
About Ibrutinib
Ibrutinib is a once-daily oral medication that blocks the BTK (search) protein, which is needed by normal and abnormal B-cells, including specific cancer cells, to multiply and spread. It is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company. Ibrutinib is approved in more than 100 countries and has been used to treat more than 300,000 patients worldwide.
About Mantle Cell Lymphoma
MCL is an aggressive type of blood cancer that originates from the B lymphocytes. The overall incidence of MCL globally is approximately 1-2 cases per 100,000 persons per year and it has a higher prevalence in men than women. MCL typically affects individuals at 65-years of age at diagnosis. While patient outcomes have dramatically improved over the latest few decades, MCL remains a difficult disease to treat with many patients relapsing or becoming resistant to therapy.