Ongoing Research Aims to Solidify CAR T-Cell Therapy’s Place in Non-Hodgkin Lymphoma

CAR T-cell therapy has proven to be an effective treatment option in non-Hodgkin lymphoma (NHL) subtypes, such as diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL), and ongoing research efforts could potentially solidify its place among other lymphoma subsets as well, according to Julie M. Vose, MD, MBA.

“[We need to] try to look at different options for our patients, with both clinical trials, as well as commercial agents, that could give [patients] a new opportunity to get a treatment that they otherwise could not have,” said Vose, who is a professor of internal medicine and division chief, Division of Oncology and Hematology, University of Nebraska Medical Center. “In some cases, we have had some amazing responses in these patients, and many of them are durable for years. We hope to bring this to more patients.”

In an interview with OncLive^® during the 2021 Pan Pacific Lymphoma Conference, Vose, who is also director of the conference, discussed the recent updates with CAR T-cell therapy and what research efforts could change the role of this type of therapy in NHL.

OncLive^®: How would you currently define the state of CAR T-cell therapy in NHL?

Vose: Currently, there are CAR T-cell therapies that are FDA approved for [patients with] relapsed or refractory DLBCL and more recently, MCL. Additionally, there are many other subtypes of NHL that they are being examined on clinical trials. [There have been some updated data] with follicular lymphoma, [as well as] different products being tested in MCL, chronic lymphocytic leukemia, and small lymphocytic lymphoma.

How could CAR T-cell therapy fit into the treatment paradigm for these other types of NHL?

Other than DLBCL and MCL, [CAR T-cell therapies for] all other types of NHL currently are on clinical trials, and they all have their very specific eligibility criteria. Typically, these patients have [progressed on] chemotherapy and immunotherapy, or other targeted products, and would be given CAR T-cell therapy as a third- or fourth-line option.

It is hard to know where [these treatments are] going to fit in in the future, but we are going to be seeing many more clinical trials. [Additionally,] we are going to be seeing them move up earlier in the course of the disease for certain patient populations, such as the high-risk DLBCL patient population.

CAR T-cell therapies for many of these different types of lymphoma have not necessarily had comparative trials yet. We do need to be able to compare them to the current standard-of-care therapies that we have and make sure that the toxicities, the outcomes, and responses are superior to other alternatives that the patient may be treated with, given their clinical situation. Those will be [studied in] upcoming clinical trials, and we also want to examine the long-term outcomes for these patients. If we see high response and remission rates, and they are durable, and what are the short- and long-term toxicity issues?

What other ongoing research or developments are you particularly excited about with CAR T-cell therapy?

In terms of future efforts for CAR T-cell therapy, as well as other types of treatments for this population of patients, there are many different options and clinical trials that are exciting. [This includes] utilizing CAR T-cell therapy in these other types of lymphomas, using them earlier in the course of the disease, and using different designs of CAR T-cell therapy with respect to whether we can alter the current modality to be able to decrease toxicity, and increase [tolerability] for patients.

It is also important to consider whether we can combine it with other agents, such as BTK inhibitors, or if we can use pre- or post-CAR T-cell therapy radiation to enhance the effects. We are also looking at different types of monoclonal antibodies, bispecific antibodies, and other new agents, either alone or in combination with CAR T-cell therapy, may be a future treatment option.

You are the director of the 2021 Pan Pacific Lymphoma Conference. What do you hope that attendees will take away from this year’s meeting?

We are trying to give an update on all the different subtypes of lymphoma to see what the current treatment options are, what we should be looking for in our patients in the near future, and some exciting clinical trials that are going on. Many of us are just trying to make sense of all the new treatment options that we have for these patients, compare them, and see what the best option is for each individual patient we see.