The Janssen Pharmaceutical Companies of Johnson & Johnson announced the Health Canada approval of IMBRUVICA® (ibrutinib) in combination with rituximab for the treatment of Waldenström's macroglobulinemia (WM). The approval expands the indication of IMBRUVICA in WM, which in 2016 became the first Bruton's tyrosine kinase (BTK) inhibitor approved for this rare blood cancer. This approval, which was expedited through a Priority Review designation by Health Canada, is for the eighth indication for IMBRUVICA in Canada. IMBRUVICA is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics, an AbbVie company. Janssen Inc. markets ibrutinib in Canada.
Waldenström's macroglobulinemia is a slow-growing and incurable form of non-Hodgkin lymphoma (NHL); its cause is unknown. Typically, patients with WM are diagnosed after developing symptoms such as anemia, fatigue and night sweats.
"WM is a rare form of blood cancer for which treatment options are limited," said Chaim Shustik, M.D., FRCP(C), Professor of Medicine, McGill University, Division of Hematology, Royal Victoria Hospital. "The latest clinical data show significant improvement in progression-free survival with IMBRUVICA in combination with rituximab, compared to rituximab alone, for both first line and later lines of treatment. IMBRUVICA offers an important new option for physicians to consider in the treatment of Canadians living with this challenging disease."
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The approval is based on results from the randomized, double-blind, placebo-controlled iNNOVATE study (PCYC-1127), the largest Phase 3 study of a non-chemotherapy combination in patients living with WM. The iNNOVATE study evaluated IMBRUVICA in combination with rituximab versus placebo plus rituximab in 150 patients with either relapsed/refractory (r/r) disease or previously untreated WM. At a median follow-up of 26.5 months, a significant improvement in the Independent Review Committee (IRC)-assessed primary endpoint of progression-free survival (PFS) was seen with IMBRUVICA plus rituximab when compared with placebo plus rituximab. Patients in the IMBRUVICA plus rituximab treatment arm experienced an 80 per cent reduction in relative risk of disease progression or death compared with patients treated with placebo plus rituximab (hazard ratio=0.20; confidence interval, 0.11-0.38, p<0.0001). The median progression-free survival was 20.3 months (95 per cent confidence interval, 13.7 to 27. months) in the placebo plus rituximab arm, and was not reached in the IMBRUVICA plus rituximab arm (95 per cent confidence interval, 35.0 months to not estimable). The data was presented in an oral session at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, selected for Best of ASCO 2018 Meetings, and simultaneously published in The New England Journal of Medicine.
The adverse reactions reported in the Phase 3 iNNOVATE study reflect treatment with IMBRUVICA plus rituximab for a median duration of 25.8 months. The most common adverse reactions (occurring in 20 per cent or more of patients with an incidence of at least 5 per cent greater than the placebo plus rituximab arm) of all grades in patients treated with IMBRUVICA plus rituximab in the iNNOVATE study were bruising (37 per cent), musculoskeletal pain (35 per cent), hemorrhage (32 per cent), diarrhea (28 per cent), rash (24 per cent), arthralgia (24 per cent), nausea (21 per cent), and hypertension (20 per cent). Grade 3 or 4 infusion-related reactions were observed in 1 per cent of patients treated with IMBRUVICA plus rituximab. The most common Grade 3/4 adverse reactions (occurring in 5 per cent or more of patients with either an all-grade incidence of at least 5 per cent greater than the placebo plus rituximab arm or a serious adverse event incidence of at least 2 per cent greater than the placebo plus rituximab arm) with IMBRUVICA plus rituximab in the iNNOVATE study were hypertension (13 per cent), pneumonia (13 per cent), atrial fibrillation (12 per cent), neutropenia (12 per cent), and anemia (11 per cent).
WM is a rare, slow-growing and incurable form of non-Hodgkin lymphoma (NHL), which comprises 1-2 per cent of all blood cancers. WM typically affects older adults and is primarily found in the bone marrow, although lymph nodes and the spleen may also be affected. Diagnosis of WM generally depends on a blood and urine test with a bone marrow biopsy to confirm. In Canada, there are an estimated 140 new cases of WM each year.