A phase 1b/2 study testing the combination of ibrutinib plus durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma (DLBCL) showed that response rates were similar to those seen with single-agent ibrutinib. Additionally, the combination resulted in added adverse events from the PD-L1 inhibitor.
“Based on initial studies that suggested promising antitumor activity with PD-1/PD-L1 blockade, we and others undertook studies to evaluate the safety and activity of anti–PD1/PD-L1–based combinations,” researchers wrote in The American Journal of Hematology. “However, subsequent studies of anti–PD-1 monotherapy have demonstrated that the single-agent response rate in FL and DLBCL is 10% or lower.”
Based on these data, the combination warrants no further study, according to the researchers.
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The study included 61 patients with follicular lymphoma (27 individuals), germinal B-cell (GCB) DLBCL (16 individuals), non-GCB DLBCL (16 individuals), and unspecified DLBCL (2 individuals). All patients were treated with once-daily ibrutinib 560 mg plus durvalumab 10 mg/kg every 2 weeks in 28-day cycles.
The overall response rate was 25%, with responses in 26% of patients with follicular lymphoma, 13% in GCB DLBCL, and 38% in non-GCB DLBCL. The 26% response rate for follicular lymphoma was similar to that of 21% seen in the phase 2 DAWN study testing ibrutinib alone, and the responses in DLBCL were similar to those previously seen with single-agent ibrutinib.
Median progression-free survival and overall survival were 4.6 months and 18.1 months, respectively, with both longer in patients with follicular lymphoma compared with DLBCL.
Immune-related adverse events were reported in 20% of patients, with 11% experiencing grade 3/4 events.
“As PD-1/PD-L1 combinations continue to be evaluated in patients with non-Hodgkin lymphoma, it will be critical to understand the biological basis for response to those agents in order to identify target populations for further study,” the researchers wrote.
Disclosure: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some of the authors disclosed financial relationships with pharmaceutical companies. For a full list of disclosures, please refer to the original study.
Reference
Herrera AF, Goy A, Mehta A, et al. Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B cell lymphoma [published online October 17, 2019]. Am J Hematol. doi: 10.1002/ajh.25659
