In the first clinical study to demonstrate the importance of precision medicine in lymphomas, researchers determined that patients with a specific molecular subtype of diffuse large B-cell lymphoma responded better to ibrutinib than patients with a different molecular subtype.
In the first clinical study to demonstrate the importance of precision medicine in lymphomas, researchers determined that patients with a specific molecular subtype of diffuse large B-cell lymphoma (DLBCL) responded better to Imbruvica (ibrutinib) than patients with a different molecular subtype.
Patients with the 2 primary subtypes of DLBCL—activated B-cell like (ABC) and germinal center B-cell-like (GCB)—who had relapsed or had not responded to prior treatment were enrolled in the trial. All patients received ibrutinib, and after a median follow-up of 11.5 months, the drug produced complete or partial responses in 37% of patients with ABC DLBCL compared with only 5% of patients with GCB DLBCL.
“Clinical trials such as this are critical for translating basic molecular findings into effective therapies,” Louis Staudt, MD, PhD, with the National Cancer Institute Center for Cancer Genomics, who co-led the study, said in a statement.
According to the study, which was published in Nature, since ibrutinib targets a key component of B-cell receptor signaling, the results of the trial provides the first clinical evidence that ABC but not GCB tumors may produce abnormal B-cell receptor signals. Current cure rates with available therapies is approximately 40% for the ABC subtype, which is worse than the rate for GCB.
As a result of the study, a phase III trial of chemotherapy with or without ibrutinib in patients with DLBCL, but not patients with the GCB subtype, is currently being conducted with the objective to determine whether or not the combination of ibrutinib and chemotherapy can increase the cure rate of patients with ABC DLBCL. According to the National Institutes of Health, this will represent the first phase III trial designed to selectively enroll patients with a particular subtype of DLBCL.
“These results support the selective development of ibrutinib for the treatment of ABC DLBCL,” the authors concluded.