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Questions Remain With CAR-T's, Checkpoints in Hematologic Malignancies

Chelsea LoCascio
Published: Monday, Nov 13, 2017

ALeo I. Gordon MD
Leo I. Gordon MD
Despite major progress with chimeric antigen receptor (CAR) T-cell therapy and immune checkpoint inhibitors in hematologic malignancies, questions remain regarding the use of these therapies in this landscape, according to Leo I. Gordon, MD.

“The question is, ‘What's going to be the role of these checkpoint inhibitors when you try to combine them with more standard treatments?’” said Gordon. “How do you combine what we know works with one of these drugs that may or may not work [with another]? There are some data suggesting that there is some added toxicity if you give a checkpoint inhibitor and then follow with allogeneic stem cell transplant.”

In an interview during the 2017 OncLive® State of the Science SummitTM on Hematologic Malignancies, Gordon, a professor of medicine at Feinberg School of Medicine, Northwestern University, and chair of the meeting, discussed promising advances and lingering challenges with novel treatments for patients with hematologic malignancies.

OncLive: There have a handful of recent FDA approvals and encouraging clinical trial results across the field of hematologic cancers. What is most notable to mention?

Gordon: In the beginning [of the conference], Dr Olga Frankfurt spoke about acute myeloid leukemia (AML). The highlight there is better understanding of the disease and better understanding of the molecular biology. The big question for AML is, “When will that translate into better outcomes?” We've been struggling with that for years, but Dr Frankfurt had some exciting data. She also spoke about novel clinical trials that are based upon some of the molecular defects that have now been uncovered. We're beginning to make progress in AML.

Myeloma is an area where there have been major advances over the years and marked improvement in outcomes in progression-free survival. There was a period of time when some of the newer drugs, newer approaches, and novel treatments were thought to perhaps be a replacement for stem cell transplant. However, recent large clinical trials have shown that we're not quite there yet.

We heard from Dr Jayesh Mehta that progress has been made. There's a good look to the future, but we're still relying on at least autologous stem cell transplant and maybe allogeneic stem cell transplant for this disease.

We heard a few words about something exciting in myeloma, and we talked about this when we got to lymphoma. That is the use of CAR T cells. There are some intriguing data from China suggesting very high response rates in patients with myeloma who are treated with CAR T cells, so more work needs to be done in that area—but we're making good progress.

The second half of the sessions started with Dr Brady Stein, who is an associate professor and is in charge of myeloproliferative neoplasms (MPNs) at Northwestern University. He sees people with MPNs, such as polycythemia vera and essential thrombocythemia. [There have been] major advances in those areas, but also a lot of confusion and different opinions about how to manage these, and very little in the way of guidelines, which we need.

He introduced some novel guidelines that have been put forth through the National Comprehensive Cancer Network and spoke about some preclinical data—data in the laboratory on aurora kinase inhibitors that may have some clinical impact very soon. There are some novel clinical trials that are emerging in MPNs, so we need a structure around those diseases.

Dr Barbara Pro, a professor of medicine in our group interested in malignant lymphomas, has a special interest in T-cell lymphomas. Those are rarer and more difficult to treat. She put together an outline of the T-cell lymphomas that highlighted some differences among them and some novel approaches to treatment. She talked about some of the clinical trials that are ongoing in that area.

Dr Jane Winter spoke about Hodgkin lymphoma. You might say, "What's to talk about with Hodgkin lymphoma? We're doing great." We're doing great in a majority of patients, but we're not doing great in all patients. There are some interesting data that suggest that the immune system may play an important role in Hodgkin lymphoma and the use of checkpoint inhibitors. These novel agents take the brakes off our own immune system in order to let our immune system attack the disease.

She discussed some novel clinical trials in 2 areas. One is in patients with relapsed/refractory Hodgkin lymphoma who are on their way to transplant. She talked about a trial utilizing the standard second-line treatment prior to transplant—which is ICE [ifosfamide, carboplatin and etoposide] chemotherapy—but adding the checkpoint inhibitor pembrolizumab to ICE. We just started a clinical trial with that and we discussed the rationale for that. We've also been using the ABVD [Adriamycin, bleomycin, vinblastine, dacarbazine] chemotherapy regimen for years.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Advances in™ Multiple Myeloma: Changing Treatment Paradigms and the Emerging Potential of CAR T-Cell TherapyAug 30, 20191.5
2nd Annual Live Medical Crossfire®: Hematologic Malignancies OnlineSep 28, 20198.0
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