On September 7, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that the European Commission (EC) has approved a variation to the marketing authorisation for IMBRUVICA (ibrutinib), extending the approved indication in chronic lymphocytic leukaemia (CLL) to include combination with rituximab for previously untreated adult patients (Press release, Johnson & Johnson, SEP 7, 2020, View Source [SID1234564703]). The decision is based on data from the Phase 3 E1912 study that showed previously untreated patients aged 70 years or younger treated with ibrutinib plus rituximab lived longer without disease progression than those treated with the established chemo-immunotherapy regimen fludarabine, cyclophosphamide and rituximab (FCR).2,3 The study was designed and conducted in the United States (U.S.) by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and sponsored by the National Cancer Institute (NCI), which is part of the U.S. National Institutes of Health.2,3
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The study evaluated 529 previously untreated patients with CLL aged 70 years or younger (median age, 58 years) who were randomly assigned to receive six cycles of ibrutinib plus rituximab (IR) (n=354), followed by ibrutinib until disease progression or unacceptable toxicity, or six cycles of FCR (n=175).2
At a median follow-up of 37 months, patients treated with IR lived longer without disease progression, with a progression-free survival (PFS) rate of 88 percent, compared to 75 percent for patients treated with FCR (hazard ratio [HR] 0.34; 95% confidence interval [CI], 0.22-0.52; p<0.0001).1 The study also showed an overall survival (OS) advantage for patients treated with the IR regimen.1 The primary study results were published previously in The New England Journal of Medicine, and with extended 48-month follow-up, as presented at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, the initial treatment benefit is maintained.2,3
"Historically, chemotherapy with FCR has been the standard of care, or first treatment prescribed for patients with previously untreated CLL," said John Gribben, MD DSc, Professor of Medical Oncology at St Bartholomew’s Hospital, Barts Cancer Institute, Queen Mary, University of London. "This decision by the EC is an important step in being able to offer patients with CLL a non-chemotherapy option in the frontline setting, building on the established efficacy and safety we have come to expect from ibrutinib-based therapy."
"We are delighted with the EC’s decision approving the use of ibrutinib in combination with rituximab for these patients," said Dr Patrick Laroche, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag. "This new non-chemotherapy combination regimen can offer extended remission, as well as fewer chemotherapy-related side effects for patients living with CLL."
Adverse events for the IR arm were consistent with the known safety profiles for ibrutinib and rituximab.1 The most common adverse reactions seen with ibrutinib include diarrhoea, neutropaenia, musculoskeletal pain, rash, haemorrhage (e.g., bruising), thrombocytopenia, nausea, pyrexia, arthralgia, and upper respiratory tract infection.4 The most common serious adverse reactions (which may affect more than 1 in 20 people) include neutropenia, lymphocytosis, thrombocytopenia, pneumonia, and hypertension.4
"Ibrutinib is the most comprehensively studied Bruton’s tyrosine kinase (BTK) inhibitor with the longest follow-up across eight positive Phase 3 trials in CLL to date, and is recognised as an important advancement in treatment for patients with CLL," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. "This latest milestone highlights our commitment to studying the full potential of ibrutinib and in developing regimens which can transform what a CLL diagnosis means for patients going forward."
This announcement comes after the U.S. Food and Drug Administration’s (FDA) approval of this expanded indication for ibrutinib in April 2020.
About ibrutinib
Ibrutinib is a once-a-day, first-in-class Bruton’s tyrosine kinase (BTK) inhibitor that is administered orally.4 Ibrutinib blocks the BTK protein; the BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signalling is needed by specific cancer cells to multiply and spread.5 By blocking BTK, ibrutinib may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.6
Indications for which ibrutinib is approved in Europe include:4
Chronic lymphocytic leukaemia (CLL): As a single agent or in combination with rituximab or obinutuzumab for the treatment of adult patients with previously untreated CLL, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy
Mantle cell lymphoma (MCL): As a single agent for the treatment of adult patients with relapsed or refractory MCL
Waldenström’s macroglobulinemia (WM): As a single agent for the treatment of adult patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy, and in combination with rituximab for the treatment of adult patients
Ibrutinib is approved in more than 99 countries for at least one indication, and to date, has been used to treat more than 200,000 patients worldwide.7
For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics for further information.
About chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is typically a slow-growing blood cancer of the white blood cells.8 The overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year and is about 1.5 times more common in men than in women.9 CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.10
The disease eventually progresses in the majority of patients, and they are faced with fewer treatment options with each relapse. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.