Emerging Therapies for Follicular Lymphoma


Nathan H. Fowler, MD: At the ASH [American Society of Hematology] 2017 meeting, we saw the results of a very interesting triplet of atezolizumab, which is a PD-L1 inhibitor, with bendamustine and obinutuzumab. A study looked at this triplet as induction therapy. Everybody got 6 cycles of therapy followed by a maintenance arm of atezolizumab given monthly and obinutuzumab given every 2 months.

They are very early data, but it looks like the overall response rate following induction therapy was very high, 80%, with a complete remission rate of 67%. The trial is still ongoing, so I think we’re going to need a little more time to look at progression-free survival to truly understand whether adding a PD-L1 inhibitor to induction therapy and maintenance could be beneficial to patients.

My colleague, Loretta Nastoupil, also presented at the ASH 2017 meeting one of the first trials to look at pembrolizumab with rituximab in patients with relapsed follicular lymphoma. In this trial, we saw response rates over 60%, along with complete remission rates over 50%. Although overall response rates were OK, it looks to me like the complete remission rate is much higher than what we see with pembrolizumab alone—actually, the pembrolizumab-alone data look like responses are only around 9%—or rituximab alone in the relapsed setting in follicular lymphoma. I think to truly interpret the data with regard to whether it’s better than single-agent rituximab will require larger studies or randomized studies.

We also saw results at the ASH 2017 meeting with a novel—novel combination of ibrutinib with a checkpoint inhibitor. These are 2 novel drugs that are very exciting and show activity in multiple hematologic malignancies. In this trial, they looked at the safety of this novel combination along with early efficacy signals. It did appear safe to combine nivolumab with ibrutinib. The overall response rate was around 30%. Now I think, like with other combinations, to understand where this will lie will require greater numbers and longer follow-up with the trial.

Carla Casulo, MD: Bendamustine and rituximab were recently evaluated in combination with idelalisib in a study that was published not too long ago in Blood Advances. That combination actually seems pretty promising for patients. This is in the relapsed setting. It suggests that combining agents might provide added benefit. But the important thing is to know that when you’re looking at combination of agents in follicular lymphoma, there can be a lot of toxicity. So, I think it’s really important that outside of a clinical trial, patients not get doublet or triplet combinations that haven’t already been studied, because you can have a lot of unanticipated toxicity.

With ibrutinib in follicular lymphoma, in and of itself, the response rates are modest: in the order of 20% to 30%. So, as a single agent, I think ibrutinib is not likely to be used, but in combination with other agents, I think it has the potential to provide additional benefit to patients with follicular lymphoma. Those studies are actually ongoing right now.

Similarly, venetoclax as a single agent in follicular lymphoma has surprisingly not been as promising as one might have hoped. But when combined with Rituxan [rituximab] or when combined with bendamustine and rituximab, studies suggest that response rates are higher and that maybe combining the agent with other things might really help it be more effective for patients.

At the ASH 2017 meeting, Kristie Blum presented data on ofatumumab and bendamustine and bortezomib in patients who have high-risk follicular lymphoma in the frontline setting. And interestingly, there’s really no difference in overall response rate or progression-free survival when you looked at each of those agents independently of one another. So, it’s not clear whether ofatumumab in combination with these other agents will be the new standard, but I think it’s important to test novel agents in the frontline setting for follicular lymphoma to see if we can improve on overall survival and progression-free survival.

Transcript Edited for Clarity

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