Photo by Larry Young
Responses to the BTK inhibitor ibrutinib differ according to a patient’s subtype of diffuse large B-cell lymphoma (DLBCL), results of a phase 1/2 trial suggest.
The study showed that patients with activated B-cell-like (ABC) DLBCL were more likely to respond to ibrutinib than patients with germinal center B-cell-like (GCB) DLBCL.
“This is the first clinical study to demonstrate the importance of precision medicine in lymphomas,” said Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.
Dr Wilson and his colleagues described the trial in Nature Medicine. The research, which was sponsored by Pharmacyclics, Inc. (the company developing ibrutinib), was previously presented at EHA 2013.
The trial enrolled 80 patients with relapsed or refractory DLBCL. All patients received ibrutinib. Tumor responses occurred in 25% of patients. There were 8 complete responses and 12 partial responses.
After a median follow-up of 11.5 months, the median progression-free survival was 1.6 months, and the median overall survival was 6.4 months.
An analysis of outcomes by disease subtype showed that ibrutinib produced complete or partial responses in 37% (14/38) of patients with ABC DLBCL but only 5% (1/20) of patients with GCB DLBCL.
The researchers speculated that ABC tumors may produce abnormal B-cell receptor signals that promote the survival of cancer cells by activating BTK, which would account for the sensitivity of ABC tumors to ibrutinib.
Based on this study’s results, researchers are conducting an international phase 3 trial of standard chemotherapy with or without ibrutinib in patients with DLBCL, excluding the GCB subtype (NCT01855750).
This is the first time a phase 3 trial has been designed to selectively enroll patients with a particular molecular subtype of DLBCL. The study’s objective is to determine if the addition of ibrutinib to standard chemotherapy can increase the cure rate of patients with ABC DLBCL.
