The European Commission ( UE ) has approved Imbruvica ( Ibrutinib ) for the treatment of adult patients with Waldenström’s macroglobulinemia ( WM ) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy.
Imbruvica is already approved in Europe for the treatment of adult patients with relapsed or refractory mantle cell lymphoma ( MCL ), or adult patients with chronic lymphocytic leukaemia ( CLL ) who have received at least one prior therapy, or in first line in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy.
Waldenström’s macroglobulinemia is a slow-growing, incurable, rare type of B-cell lymphoma. Waldenström’s macroglobulinemia begins with a malignant change to the B cell during its maturation so that it continues to reproduce more malignant B cells. WM cells make large amounts of a certain type of antibody ( immunoglobulin M, or IgM ). Antibodies such as IgM normally help the body to fight infection. Excess IgM causes the blood to thicken and causes many of the symptoms of Waldenström’s macroglobulinemia, including among others excess bleeding and problems with vision and the nervous system.
The median age at diagnosis is 63-68 years and incidence rates among men and women in Europe are approximately 7.3 and 4.2 per million persons, respectively.
Genome sequencing of patients with Waldenström’s macroglobulinemia has revealed a common mutation in the MYD88 gene. This mutation triggers the activation of the enzyme Bruton’s tyrosine kinase ( BTK ), which is a key component needed to regulate immune cell proliferation and cell survival which plays a part in B-cell malignancies, such as Waldenström’s macroglobulinemia .
Imbruvica forms a strong covalent bond with BTK, thereby inhibiting the enzyme and blocking the transmission of cell survival signals within the malignant B cells.
The phase 2 multi-centre study on which the approval was based evaluated the efficacy and tolerability of Imbruvica 420 mg once daily in 63 patients with previously treated Waldenström’s macroglobulinemia ( median age of 63; range, 44-86 years old ).
Updated results from the study were published in The New England Journal of Medicine ( NEJM ).
The overall response rate using criteria adopted from the International Workshop on Waldenström’s macroglobulinemia was 90.5%, 57 out of 63 patients.
Eleven patients ( 17% ) achieved a minor response, 36 patients ( 57% ) achieved a partial response ( PR ) and 10 patients ( 16% ) achieved a very good partial response. The median times to at least minor and partial responses were four weeks and eight weeks, respectively.
Secondary endpoints included progression free survival and the safety and tolerability of Imbruvica in symptomatic patients with relapsing/remitting Waldenström’s macroglobulinemia.
The estimated two–year progression-free survival and overall survival rates among all patients were 69.1% and 95.2% respectively.
The most commonly occurring adverse reaction in the WM trial ( 14 patients, or 22% ) was neutropenia. Thrombocytopenia occurred in nine patients ( 14% ), and other adverse events occurred in less than five patients ( less than 10% ) each.
Four patients ( 6% ) in the trial receiving Imbruvica discontinued treatment due to neutropenia or thrombocytopenia. Additionally these two adverse events lead to dose reduction in three patients ( 5% ). ( Xagena )
Source: Janssen, 2015