A Type II variation application seeking the approval of a new indication for ibrutinib plus bendamustine and rituximab in adult patients with previously untreated mantle cell lymphoma who are not candidates for autologous stem cell transplant has been submitted to the European Medicines Agency.
A Type II variation application seeking the approval of a new indication for ibrutinib (Imbruvica) plus bendamustine and rituximab (Rituxan; BR) in adult patients with previously untreated mantle cell lymphoma (MCL) who are not candidates for autologous stem cell transplant (ASCT) has been submitted to the European Medicines Agency.1
The application is supported by findings from the phase 3 SHINE trial (NCT01776840), in which the ibrutinib combination significantly improved progression-free survival (PFS) vs BR alone in patients with newly diagnosed MCL who were aged 65 years or older.
Data from the trial, which met its primary end point, will be shared at an upcoming medical conference, according to a press release issued by the Janssen Pharmaceutical Companies of Johnson & Johnson.
“MCL can be a difficult blood cancer to treat, and despite progress in this area of the last few years, an unmet need remains for new treatment approaches,” Edmond Chan, MBChB, MD (Res), EMEA therapeutic area lead haematology, at Janssen-Cilag Limited, stated in a press release. “This submission to the EMA is a testament to our commitment to deepening the impact ibrutinib can have for patients and represents an important step toward providing patients and health care professionals with the addition of targeted therapy to standard therapy.”
SHINE enrolled patients with a diagnosis of MCL who had clinical stage II, III, or IV disease by Ann Arbor classification.2 To be eligible for participation, patients needed to have at least 1 measurable site of disease, an ECOG performance status of 0 or 1, and they could not have received prior treatment for their disease.
If patients underwent major surgery within 4 weeks of randomization, had known central nervous system lymphoma, a history of stroke or intracranial hemorrhage within 6 months before random assignment, required anticoagulation with warfarin or another vitamin K antagonist or strong CYP3A inhibitors, they were excluded. Those for whom the goal of treatment was tumor debulking before stem cell transplant, were also excluded.
Approximately 520 patients were randomized 1:1 to the investigative or comparator arms. All patients were given open-label BR background treatment for a maximum of 6 cycles, and those who achieved a complete response (CR) or partial response (PR) continued to receive open-label background therapy with rituximab maintenance every second cycle for up to 12 additional doses. In addition to this background treatment, patients received ibrutinib or placebo.
Bendamustine was given intravenously (IV) at a dose of 90 mg/m2 on days 1 and 2 of cycles 1 through 6. IV rituximab was delivered on day 1 of cycles 1 through 6 at a dose of 375 mg/m2, and if a CR or PR was achieved, it was given at the same dose on day 1 of every second cycle for up to 12 additional doses. Ibrutinib was given orally, at a once-daily dose of 560 mg, continually starting on day 1 of cycle 1.
Study treatment was given until progressive disease, intolerable toxicity, or study completion.
Those who achieved stable disease following initial chemoimmunotherapy continued to receive ibrutinib or placebo until progressive disease, intolerable disease, or study end. Patients who experienced disease progression needed to discontinue study treatment.
The primary end point of the trial was PFS, and secondary end points included overall survival, overall response rate, minimal residual disease negativity rate, duration of response, time to next treatment, toxicity, and other pharmacokinetic measures.
“As the first approved BTK inhibitor, ibrutinib has now been used to treat more than 250,000 patients globally. It is also the first BTK inhibitor to be studied as a frontline treatment option for patients with MCL,” Craig Tendler, MD, global head of late development, Diagnostic & Medical Affairs, Hematology & Oncology, at Janssen Research & Development, LLC, added in the press release. “We are committed to the continued development of ibrutinib in B-cell malignancies where unmet needs remain in our efforts to make meaningful differences and change outcomes for patients.”