A combination of ibrutinib, lenalidomide, and rituximab was tested on patients with relapsed or refractory diffuse large B-cell lymphoma, particularly those with non-GCB subtype.
The combination of ibrutinib, lenalidomide, and rituximab was safe and had promising activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), particularly those patients with non-GCB (germinal center B-cell–like) subtype, according to a phase 1b study published in the journal Blood.
Based on these results, the triplet combination “warrants further evaluation in this patient population with a significant unmet medical need,” wrote Andre Goy, MD, of John Theurer Cancer Center at Hackensack University Medical Center, and colleagues in Blood.
The phase 1b portion of the dose-escalation study enrolled transplant-ineligible patients with relapsed or refractory DLBCL. Patients received once-daily 560 mg ibrutinib, 375 mg/m2 rituximab, and 10, 15, 20, or 25 mg lenalidomide. About half (51%) of patients had non-GCB DLBCL, and 33% had transformed disease.
Of 12 patients enrolled in cohort 1 at the 15-mg lenalidomide dosage, 3 patients had dose-limiting toxicities. Because of this, a de-escalation cohort was initiated at 10 mg lenalidomide. At this dose, one dose-limiting toxicity occurred, prompting re-escalation to the 15-mg lenalidomide dose with additional toxicity management guidelines.
Escalation to the 20-mg and 25-mg dose of lenalidomide resulted in zero dose-limiting toxicities. The maximum-tolerated dose was not reached.
Safety with the triplet regimen is similar to what was seen for each of the individual drugs, according to the researchers.
The overall response rate with ibrutinib, lenalidomide, and rituximab was 38%, with an increase to 44% looking at only response-evaluable patients. The researchers noted that only two responses occurred at the 20-mg lenalidomide dose, but added that it “may be due to a large variation from the small number of patients in this cohort” and that phase II evaluation of this dose may reveal more robust efficacy.
In those patients with the non-GCB subtype, the overall response rate was 65% among response evaluable patients with 41% having complete response. In contrast, the overall response rate was 29% in patients with GCB subtype.
The researchers noted that the study was not powered to compare subpopulations.
“These findings are noteworthy because responses are traditionally higher with salvage chemotherapy in GCB versus non-GCB DLBCL patients, as the most common subtype (2/3 cases) in elderly patients,” the researchers wrote.
The median duration of response overall, and for patients with non-GCB subtype, was 15.9 months. Two patients have been on therapy for longer than 3 years.
A phase 2 trial was initiated with the 20-mg dose of lenalidomide because the phase 1 cohort of 25 mg was still ongoing. An addition cohort at 25 mg has been added to the phase 2 study.