DR FLOWERS: So when we look at idelalisib, that is an agent that has been approved either as a single agent in follicular lymphoma or approved in combination with rituximab for patients with CLL. This is an approach to try and look at whether that agent can also be combined with chemotherapy.

There have been concerns about combining idelalisib, particularly with other novel agents, where we have seen some unexpected toxicity in some early-phase clinical trials. And so particularly in the combination with lenalidomide. So this is a look at trying to combine it with chemotherapy and randomized patients to idela plus BR versus BR alone.

In this trial, what they found is that all of the patients were able to get through their BR therapy, either alone or with idela. And then patients went on to idela monotherapy after that.

When you look at the overall survival that was seen in this trial, the median overall survival for patients with idela plus BR was not reached, versus 41 months for the BR. When you think about BR in patients with CLL, that overall survival is about on par with what you might expect for this population.

And so this provides data that you could use this in combination as a superior regimen, at least in terms of overall survival, for patients with relapsed and refractory CLL. I think, again, these are data that we need to see longer follow-up, particularly given some of the toxicities that we’ve seen with idela, either in other trials or with longer follow-up — with idela, in particular the PJP that has been a concern and the toxicity such as pneumonitis and the gastrointestinal toxicities like inflammatory diarrhea.

So we’ll need to see, kind of with longer follow-up on these trials, on this particular trial, whether those things might be issues for those patients. If they are not, this may be an option as opposed to BR.

DR LOVE: Right now, how do you incorporate idelalisib in your practice? And where do you see things heading that — you mentioned the concerns about toxicity.

DR FLOWERS: So I typically use idelalisib as an agent in relapsed and refractory follicular lymphoma, as an option in the relapsed setting for patients who want a standard of care oral therapy. And in CLL, it’s an option that I consider for patients most commonly after they’ve had ibrutinib and either come off ibrutinib for toxicity reasons or have failed ibrutinib. I think now, with venetoclax falling into that space, particularly for the 17p population, I think it’s something that you need to think about, how you would sequence those 2 therapies, but it’s something that I typically use in later lines of therapy for patients with CLL.

DR LOVE: I mean, is there active interest in this agent in terms of current ongoing trials?

DR FLOWERS: There is. And I think these data at least speak to that, how it would be used in combination. I think how it’s going to be used in patients with follicular lymphoma, we’ll need additional data to be able to support that. There is the need for randomized controlled trials, though, to confirm the Phase II results that led to the accelerated approval in follicular lymphoma.

This drug is the first approved PI3 kinase inhibitor. And so it’s an agent that, if we can figure out how best to use it, I think does have benefit for patients. I’ve seen patients with CLL who’ve had good responses. I’ve seen patients with follicular lymphoma and actually had a number of patients with follicular lymphoma who’ve had very durable responses on the original pivotal trial in follicular lymphoma.

So I think it has benefits. I think we need to weigh those benefits with toxicity. And there are many other approaches like allogeneic stem cell transplantation, like CAR T-cell therapies and other aggressive chemotherapy agents — chemotherapy approaches where we know that there are significant toxicities associated with that approach and we weigh the benefits of the approach versus the toxicity. I think that’s an important thing that we’ll need to do for idelalisib in terms of how we sequence it and where we place it.

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