EHA 2016
Evaluation of ibrutinib in treatment of CLL with 17p deletion
Dr Jeffrey Jones - OSU James Cancer Hospital, Columbus, USA
Thank you for the opportunity to present the results of an integrated analysis across several trials involving deletion 17p patients with chronic lymphocytic leukaemia. While chronic lymphocytic leukaemia is generally considered an indolent lymphoid malignancy, prognosis is quite heterogeneous and patients with deletions of chromosome 17p in particular experience a relatively dismal prognosis historically. Historical data suggests that those patients live only 2-3 years beyond the initiation of therapy.
Ibrutinib, a first in class oral once daily inhibitor of the Bruton’s tyrosine kinase, is a therapy with marked activity in deletion 17p CLL that allows for treatment of the disease without utilisation of chemotherapy. The drug is now approved in both the US and Europe for various CLL and small lymphocytic lymphoma indications, specifically including patients with deletions of chromosome 17p. So this integrated analysis tries to provide a more robust estimate of clinical outcomes among ibrutinib treated patients with deletion 17p CLL.
Three large multicentre trials were included in the analysis and we limited the analysis to patients with deletion 17p identified by fluorescence in situ hybridisation, a very standard technique. 243 patients were included, all of whom received once daily oral ibrutinib. The majority were treated at the now standard dose of 420mg daily with a smaller number, only 11, treated at a higher dose of 840mg. As in other studies of ibrutinib, all patients received treatment until progressive disease or until discontinuation for unacceptable toxicity. The primary endpoints of this analysis were the overall response rates and survival endpoints, both progression free and overall survival as well as severe, that is three or greater adverse events of specific clinical interest. At the time of this analysis the median time on study was 28 months. The key findings of our analysis are demonstrated here, first in the panel on the right you can see that an overall response was achieved in 84% of patients including a minority, 9%, who achieved a complete remission. At 30 months of follow up an estimated median progression free and overall survival had not yet been reached. At that 30 month time point 55% of patients remained progression free and 67% of patients remained alive.
Again, with a median time on study of 28 months in this group of 243 patients with high risk CLL, all of whom had deletion 17p, the estimated 30 month progression free and overall survival surpassed those reported for all other existing therapies for deletion 17p CLL. Overall response rate was consistent across studies, approximately 84% in all of the studies included here. Finally, with respect to adverse events the severe adverse events declined over time and only 15% of patients discontinued therapy because of an adverse event. At the time of the analysis 45% of patients remain on study treatment with ibrutinib.
