The combination of ibrutinib (Imbruvica®), lenalidomide (Revlimid®), and rituximab (Rituxan®) had a manageable safety profile and demonstrated durable activity in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a study published in Blood.
In the phase Ib portion of the open-label, dose-escalation study, researchers assessed the maximum tolerated dose (MTD) and preliminary safety and activity of the triplet regimen in transplant-ineligible adults with histologically confirmed relapsed/refractory DLBCL.
A total of 45 patients (median age, 64 years) received ibrutinib 560 mg daily, rituximab 375 mg/m2 intravenously on day one of cycles one through six, and lenalidomide (10 mg, 15 mg, 20 mg, or 25 mg) on days one to 21 of each cycle. The median time from diagnosis was 14.1 months. Patients had non-germinal center B-cell (non-GCB; 51%) DLBCL and transformed DLBCL (33%). Many patients (60%) had refractory disease. Median follow-up was 25.6 months (range, 0.4-44.8 months).
Following dose-limiting toxicities at the lenalidomide 15 mg level, patients were de-escalated to receive lenalidomide 10 mg and, following subsequent re-escalation to lenalidomide 25 mg, the MTD was not reached.
Nearly 50% response rate with triplet therapy
Among eligible patients, the overall response rate (ORR) was 44% (n=39; 95% CI, 28-60), including a complete response rate of 28%. Specifically, the ORR was 65% in non-GCB patients (n=17), 69% in relapsed patients (n=16), and 56% in secondary refractory patients (n=27).
The overall median response duration was 15.9 months, and two patients continued on therapy beyond three years.
The most common treatment-related adverse events were gastrointestinal events, myelosuppression, fatigue, hypokalemia, peripheral edema, and maculopapular rash.
Phase II of the study is ongoing.