Ibrutinib is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor that has been approved as monotherapy for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and for CLL with a deletion in chromosome 17p (del17p), based on phase 3 safety and efficacy data (Byrd JC, et al. N Engl J Med. 2014;371:213-223). Allogeneic stem-cell transplantation (SCT) is also used to treat patients with CLL, especially those at high risk, and patients who relapse after allogeneic SCT are difficult to treat with chemotherapy because of their impaired hematopoietic stem-cell reserve and infections. At ASH 2014, Coutre and colleagues reported on an analysis of the safety and efficacy of ibrutinib in patients with CLL who relapsed after allogeneic SCT (Blood. 2014;124. Abstract 4697).
Data were collected from 16 patients with relapsed or refractory CLL who had undergone allogeneic SCT and were subsequently treated with ibrutinib alone or in combination with ofatumumab. Del17p and a deletion in chromosome 11q (del11q) were reported in 10 and 3 of these patients, respectively. The median time since the most recent allogeneic SCT was 27 months, and some of these patients had received salvage therapy between allogeneic SCT and ibrutinib. After a median follow-up of 23 months, the overall response rate (ORR) was 87%, with 2 complete responses (12%), 9 partial responses (56%), and 3 partial responses with lymphocytosis (19%). The median duration of response, progression-free survival (PFS), and overall survival (OS) were not reached during this follow-up period, with 24-month PFS and OS rates of 77% and 75%, respectively. Grade 3/4 adverse events (AEs) were noted in 11 patients (69%), with the majority comprised of infections.
These data support the use of ibrutinib in patients with CLL and previous allogeneic SCT, as well as the exploration of its use for chronic graft-versus-host disease, which is the subject of an ongoing clinical trial.
