Ibrutinib for Diffuse Large B Cell Lymphoma – pro
On July 28, 2014, the U.S. Food and Drug Administration approved Imbruvica (ibrutinib) to treat patients with chronic lymphocytic leukemia (CLL) who carry a deletion in chromosome 17 (17p deletion), which is associated with poor responses to standard treatment for CLL. It had a prior approval for mantle cell lymphoma and CLL patients as second line. Imbruvica received a breakthrough therapy designation for this use. based on a clinical study of 391 previously treated participants, 127 of whom had CLL with 17p deletion. Participants were randomly assigned to receive Imbruvica or Arzerra until disease progression or side effects became intolerable.
The trial was stopped early for efficacy after a pre-planned interim analysis showed Imbruvica-treated participants experienced a 78 percent reduction in risk of disease progression or death (progression-free survival). Results also showed a 57 percent reduction in risk of death (overall survival) in participants treated with Imbruvica. Of the 127 participants who had CLL with 17p deletion, those treated with Imbruvica experienced a 75 percent reduction in risk of disease progression or death.
It is currently only approved for mantle lymphoma, CLL and Waldenstrom’s. In regard to Diffuse Large B Cell Lymphoma, there is one reported study. In a phase Ib study in 22 treatment-naive diffuse large B-cell lymphoma patients, 100% of subjects responded to the combination of ibrutinib at 560 mg/d plus standard R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone), given for six cycles. Complete responses were observed in 91% and partial responses in 9. Serious adverse events were reported in 12 patients, most commonly febrile neutropenia (17%).
A phase III trial of R-CHOP plus ibrutinib is ongoing in a select group of patients with de novo, treatment-naive non–germinal-center B-cell–like diffuse large B-cell lymphoma.
Wilson WH, Young RM, Schmitz R, et al. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma [published online July 20, 2015]. Nat Med. doi: 10.1038/nm.3884. – See more at: http://www.onclive.com/web-exclusives/ibrutinib-induces-impressive-response-in-dlbcl-subtype#sthash.KtMZYFwd.dpuf
Younes A, Flinn I, Berdeja J, et al: Combining ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP): Updated results from a phase 1b study in treatment-naïve patients with CD20-positive B-cell non-Hodgkin’s lymphoma. 2013 ASH Annual Meeting. Abstract 852. Presented December 10, 2013.
Ibrutinib, Prescribing Information 2016