An Overview of B-Cell Malignancies

A comprehensive review of the individual diseases that constitute B-cell malignancies.

Transcript

Michael A. Kolodziej, MD: The American Society of Hematology [ASH] meeting every year often has a wide variety of presentations on malignant hematology. There’s all this information about sickle cell disease and thrombosis. That’s not what we’re going to talk about. What we are talking about is malignant hematology and more specifically within malignant hematology, lymphoma, for all intents and purposes.

Now, when you talk to hematologists about lymphoma, the first thing that they think about is diffuse large B-cell non-Hodgkin lymphoma. That’s the most common subtype of non-Hodgkin lymphoma, and there were some presentations at the meeting about that. And then there’s a large group of lymphomas, very heterogeneous, called follicular lymphomas. We’re not going to really spend much time on those.

And then there are these other hematological malignancies, B-cell neoplasms, that have in general a more indolent course. There’s a ton going on in those diseases right now, both presented at the ASH meeting and then in and around the ASH meeting. We’d be remiss not to mention plasma cell neoplasms, multiple myeloma, which has been a particularly active area the last couple of years and was highlighted at the ASH meeting.

So, if we talk briefly about diffuse large B-cell lymphoma first, I was talking to somebody the other day and we haven’t really done anything interesting in diffuse large B-cell lymphoma since we got Rituxan in 1997—that’s a long time ago—until chimeric antigen receptor T-cell therapy [CAR T], and CAR T changed everything. We are still figuring out CAR T, and there were a lot of presentations at the meeting about CAR T and diffuse large B-cell non-Hodgkin lymphoma, most specifically about the durability of response. We have not yet realized the full potential of those malignancies. I think there’s a couple of reasons for that. One is that CAR T remains largely locked within the inpatient setting. That makes access somewhat of a challenge. The second thing is that we frankly don’t know how to pay for it. Diffuse large B-cell lymphoma is a disease of older patients, and Medicare reimbursement for CAR T is frankly inadequate, and that has really hindered the ability to treat patients with CAR T. But hopefully we’ll figure that out.

Interestingly, there was a presentation looking at a bifunctional antibody. CAR T is complicated because making CAR T is complicated, and it’s expensive to make it. So people have been interested in these “off-the-shelf” solutions. One of them is a bifunctional antibody that was reported in patients with relapsed/refractory non-Hodgkin lymphoma, including patients who had failed CAR T, and the results were very remarkable. I don’t know if they’re going to prove to be durable. That’s going to be a recurring theme in our talk today, I think. But that’s tremendously exciting. That’s what’s largely happening in diffuse large B-cell lymphoma.

There wasn’t that much about follicular lymphoma, but then we’ve got this other group of disorders. We’ve got chronic lymphocytic leukemia/small lymphocytic lymphoma. We’ve got Waldenstrom macroglobulinemia. We’ve got mantle cell lymphoma. I talk as if they’re all lumped together. That’s not true, but there’s been a tremendous improvement in our treatment options for patients with those conditions, particularly in the relapsed and the refractory setting. But increasingly, those therapies are moving to the frontline setting, and that will likely change the way we treat those disorders.