ASH 2015: For Lymphoma, CLL, the Action Is in Combinations

Bruce D. Cheson, MD


December 03, 2015

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Hey, there. This is Bruce Cheson from Georgetown University Hospital, speaking to you for Medscape Hematology. It's that time of the year again: the American Society of Hematology (ASH) Annual Meeting preview for 2015.

I guess the people at ASH feel obliged to give us a few chemotherapy studies. There will be the third iteration of RCHOP-14 vs RCHOP-21 in diffuse large B-cell lymphoma. Will it be any better this time around?

As you know, there are two basic types of diffuse large B-cell lymphoma. There is the ABC, or activated B-cell type, and the germinal center type. The activated B-cell type traditionally does not do as well with standard therapy. However, certain drugs are preferentially active in this subtype, such as ibrutinib, lenalidomide, and bortezomib. At ASH, we're going to see the first results in large cell lymphoma of RCHOP with or without bortezomib in this population. Will it improve outcomes? I will not spoil the suspense.

We're also going to see results of bortezomib as either consolidation or maintenance following aggressive chemotherapy for untreated mantle cell lymphoma. There are interesting data there as well.

But what everybody wants to hear about are the novel targeted drugs. They're not even so novel anymore; there are so many of them out there. They want to hear about the non-chemotherapy approach for patients with lymphoma and chronic lymphocytic leukemia (CLL). There will be some single-agent data, including ibrutinib vs chlorambucil—the RESONATE-2 trial.

They're always trying to beat up chlorambucil. It's like the sick puppy out there that always gets drugs approved because everything is better than chlorambucil. We'll see in this trial with untreated CLL patients that the results are extremely impressive.

We'll see the results of ibrutinib in relapsed refractory follicular lymphoma. There was a previous abstract that showed a response rate of 28%, but there may be implications of a dose-response effect. Stay tuned for that one. We'll see the results of ibrutinib vs temsirolimus in mantle cell lymphoma, and we will see the results of venetoclax, or ABT-199, in CLL and non-Hodgkin lymphoma.

And now, we're into the second- and third-generation drugs. We're going to see some very exciting data on ACP-196, the new BTK inhibitor, in patients with relapsed refractory CLL. We will also see the idelalisib frontline data in chronic lymphocytic leukemia. There are lots of interesting single agents, but that's not where the action is, my friends.

The action is in combinations. We will see ibrutinib and rituximab in untreated follicular lymphoma. We're going to see a regimen that we developed in Alliance with R-squared: rituximab plus lenalidomide plus ibrutinib in untreated follicular lymphoma. We'll see various agents in combination with bendamustine, rituximab, bendamustine and rituximab, and we will also see venetoclax and the second-generation anti-CD20 antibody obinutuzumab. Promising data.

Speaking of obinutuzumab, it was approved for CLL on the basis of the CLL11 trial, in which it was rituximab/chlorambucil vs obinutuzumab/chlorambucil vs chlorambucil. Both combination arms were better than chlorambucil, but the obinutuzumab arm appeared to be superior to the rituximab arm. Okay, that's nice, but why don't we use a regimen in a study that's actually used to treat patients in this country? Well, we'll see preliminary data from the GREEN trial, in which there will be, as one of the arms, bendamustine and obinutuzumab. Let's see what happens with that study.

The excitement continues to mount for another class of drugs: the checkpoint inhibitors. There are lots of these in clinical trials. We saw at the last ASH meeting some astounding data with nivolumab in relapsed/refractory Hodgkin lymphoma and with pembrolizumab in a similar population. We will see at this meeting an update of those data. Do they really hold up over time? Let's hope so.

Again, combinations are where it's at. There will be a presentation on brentuximab vedotin (Adcetris®), the anti-CD30 antibody drug conjugate, plus a checkpoint inhibitor in relapsed/refractory Hodgkin's lymphoma. Those data will be of particular interest to me because I'm getting ready to activate a study of brentuximab vedotin plus nivolumab in patients with untreated Hodgkin disease. We'll also see data on checkpoint inhibitors in the treatment of patients with that really awful condition, Richter transformation.

I hope to see you in Orlando. Perhaps you'll also see this friend of mine. Excuse me while I move this camera. There he is. He's vacationing for the winter there, so Mr Mick and I will be running into you down there. Have a good ASH meeting, for those of you who go. For those of you who don't, we'll have a wrap-up session with Medscape Hematology afterwards.

Thank you very much. See you there. Bruce Cheson, signing off.


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