Combining Targeted and Immunotherapeutic Agents in FL

Transcript:Shuo Ma, MD, PhD: One study I want to mention is a combination study of ibrutinib with rituximab in previously untreated follicular lymphoma patients. In the past, there was a study reporting single-agent ibrutinib in relapsed/refractory follicular lymphoma with a response rate of about 30%, showing some activity in lymphoma. But the modest response rate was not ideal, so therefore, the combination has the potential to improve that.

Dr. Fowler, at ASH 2015, is reporting an abstract combining immunotherapy with rituximab and ibrutinib in treatment-naive follicular lymphoma patients. This is the phase II multicenter study that included patients who have previously untreated follicular lymphoma, with 60 patients included. The median age of the patients was 58 years. Patients had follicular lymphoma grade 1, 2, or 3A. Grade 3B was excluded in this study.

All of the patients met the criteria for needing treatment for follicular lymphoma. Patients received ibrutinib at 560 mg once daily, and continued until disease progression or until intolerable toxicity. In addition, rituximab was given weekly 4 times at a standard dose of 375 mg/m2 starting from week one. So, the combination was the first four weeks and then after that, patients continued monotherapy with ibrutinib.

The primary endpoint of the study is overall response rate. After about 10 months of the median follow-up time, the overall response rate for these patients was reported to be 80% with about 30% complete response. The toxicity of the patients treated was pretty similar to single-agent ibrutinib, with no significant unexpected toxicity with the addition of rituximab.

So the take-home message is that a combination of ibrutinib with rituximab is a very effective treatment for previously untreated follicular lymphoma patients, and the combination has a high response rate with a 30% complete response, and the toxicity profile is very similar to single-agent ibrutinib.

Ibrutinib has been studied in various types of B-cell lymphomas because of its action on the B-cell receptor pathway. As we have discussed, there are studies in follicular lymphoma, but there are also ongoing studies in other indolent lymphomas. There's one ongoing phase III study combining ibrutinib with two immunochemotherapy regimens, either rituximab, bendamustine, or R-CHOP. These are conducted in patients with follicular lymphoma and marginal zone lymphoma.

Transcript Edited for Clarity