Promising treatment developments in lymphoma immunotherapies

Immunotherapies are showing early promise against B-cell lymphomas and researchers are starting to turn their attention to the possible benefits of combination immunotherapies.

Managed Healthcare Executive (MHE) spoke with Helen E. Heslop, MD, DSc (Hon.) of the Baylor College of Medicine and Texas Children’s Hospital in Houston, who co-chaired a lymphoma session at the 58th American Society of Hematology (ASH) Annual Meeting in San Diego on Sunday. December 4.

MHE: What is new in the field of lymphoma immunotherapies, this year?

HeslopHeslop: The main take-homes are there are a lot of immune checkpoint inhibitor studies this year and T-cell therapies for lymphoma. For T-cell therapies, there are two major T-cell therapies. The first are T cells that can target native receptors, T cells that seek viruses or tumor antigens. And then obviously are the CAR [chimeric antigen receptor]-T cells.

I think CAR T-cells for lymphoma don’t have quite the same high response rate they have in leukemia. Overall, it’s about 50% to 80% compared to 90%, and there are slight differences between the different types of lymphoma.

But I think nevertheless it’s very encouraging. Looking at what’s published in Kite’s Phase 2 [ZUMA-1] trial, it says it’s a lot better than standard therapy so I would hope that one of the CD-19 CARs will be licensed for lymphoma in the next year.

Editor’s note: The Zuma-1 trial will be discussed during a late-breaking abstract session at ASH on Tuesday, December 6.

MHE: Which patients are candidates for CD-19 CAR T-cell therapies?

Heslop: This was for B-cell lymphomas. One of the things that is not available at the moment is a therapy for T-cell lymphoma, where there might be more of an unmet need. For the present, the data looks at B-cell lymphomas targeting CD19. There were responses in different sorts of B-cell lymphomas, like diffuse large B-cell lymphoma. So I think that those will be the indications that are approved.

What is impressive about the study is that they’re targeting a population of treatment-refractory lymphoma where a previous interim analysis had shown that only about 8% of patients are going to get a complete response-and they’re seeing a 47% complete-response rate. That’s a huge difference for this patient population that doesn’t have other good options.

Of course, the question now is how long these responses are going to be sustained. They don’t have that data yet.

MHE: Has there been progress for immune checkpoint inhibitors in lymphoma? What’s new there?

Heslop: There are a lot of abstracts this year on immune checkpoint inhibitors. Some of them are updating studies with Hodgkin’s where there were promising initial responses; they are being sustained in larger studies. Some of them have got responses that have persisted for longer times of time, now, which is encouraging.

What I think is also encouraging is that in some smaller studies, they’re extending it to other lymphomas that overexpress PD-L1, so the response rates are not quite so high but are encouraging in primary mediastinal B-cell lymphoma and also in mycosis fungoides and Sézary syndrome, which is particularly hard to treat. And there’s a very small study where they’ve got a very good response rate in primary CNS and follicular lymphoma, which are hard to treat. I think all of those findings are interesting.

MHE: Are there biomarkers available to identify the patients with lymphoma who might benefit from immune checkpoint inhibition therapy?

Heslop: The one that has been interesting is that Hodgkin’s disease, which responds very well, has abnormalities in chromosome 9, which lead to overexpression of PD-L1 and PD-L2. These are abnormalities that are now being found in other lymphomas, that are now being targeted, with response rate. I think that’s interesting.

MHE: Is there reason to believe combination immunotherapies will prove promising against lymphoma?

Heslop: That’s obviously the next place to go. So combination of different types of checkpoint inhibitors and in combinations, obviously, with T cells and checkpoint inhibitors and with other small molecules. There aren’t many abstracts on that yet but people are beginning to design studies. It’s early days but I think there’s a lot coming through. Probably next year we’ll see a lot of abstracts on combinations.