CD19-Directed Antibody-Drug Conjugates for DLBCL

Part 1: Real-World Barriers to CAR T-Cell Therapy in Advanced DLBCL

During a live virtual event, Jason Westin, MD, discussed the challenges of giving patients access to chimeric antigen receptor T-cell therapy.

DISCUSSION QUESTIONS

  • What are the real-world challenges with chimeric antigen receptor (CAR) T-cell therapy in the community setting?
  • What is your access to CAR T therapy? How feasible is it (logistically) for your patients? ​
  • Who is involved in decision making regarding CAR-T therapy versus stem cell transplant (SCT)?​
  • Are there specific groups/types of patients you would not want to refer for CAR T-cell therapy? ​

JASON WESTIN, MD: Let’s talk about the real-world challenges with CAR T-cell therapy in the community setting, things we just mentioned: access, cost, cell collection, and length of hospital stay. Dr Hasanov, what is your access to CAR T-cell therapy, and how feasible, logistically, is it for your patients to gain access?

ELSHAD HASANOV, MD: I’m a medical oncology fellow at [The University of Texas] MD Anderson Cancer Center. At MD Anderson, [we have access], but in the MD Anderson oncology program at Lyndon B. Johnson [LBJ] Hospital, it’s a bit challenging. So, it’s hard for me to answer the questions for either of the sites. But it’s basically not possible for those patients at the LBJ Hospital site.

WESTIN: Outside of the auspices of MD Anderson, how does that work? Like you said, there are situations where you can potentially see a CAR T-cell therapy center from your back door but may not be able to get there, in terms of logistical access. Dr Malik, have you had an opportunity to refer for a patient for CAR T-cell therapy?

HENNA MALIK, MD: I’m in community practice at Texas Oncology in Houston. So, I’m not too far from MD Anderson, it’s just running the logistics and seeing the performance status of the patient, how strong they are. That’s usually what hinders us getting them down to autologous SCT or to CAR T-cell therapy. It also depends on their insurance plan, because a lot of the plans Texas Oncology takes, MD Anderson doesn’t accept. So, that’s also a hindrance for these patients. So, it just depends on their insurance and their performance status. I haven’t had a patient yet that I’ve referred, just because they’ve been too weak around third-line treatment to be evaluated for CAR T cell.

WESTIN: I think there is a Goldilocks pattern here, where you have to get a patient before they’re too sick, but obviously you can’t send them when they’re [in perfect shape]. It’s making sure that you’re getting access at a time point that’s relevant for the patient. Dr Anderlini performs the apheresis procedure for a lot of these patients. But, Dr Anderlini, I know you know the data quite well for CAR T-cell therapy compared with other options. In our transplant department, we’re believers in cell therapy. But how do you view CAR T-cell therapy fitting into the regimens for second-line and third-line patients with large-cell lymphoma?

PAOLO ANDERLINI, MD: As you pointed out, I have somewhat of a skewed point of view here, because working at MD Anderson, we have access to CAR T-cell therapy. But as a transplanter, however, I think it’s going to be some brainstorming and serious thinking after physicians look at the plenary session at the American Society of Hematology 2021 Annual Meeting with the primary analysis of the ZUMA-7 trial [NCT03391466]. The results suggest comparing CAR T-cell therapy versus standard-of-care therapy, including SCT. So I think that there may be some second thoughts as far as whether CAR T-cell therapy should be considered or not.

WESTIN: Dr Obi-Anyadike, what’s been your experience with the CAR T-cell therapy, in terms of referring your patients, and how has that fit into your practice?

GLORIA OBI-ANYADIKE, PHD: I’m in an academic, transplant, and CAR-T therapy center. So, we do offer a variety of CAR T-cell therapies for DLBCL. For the most part, it’s been good experience in terms of some of these patients doing very well with CAR T-cell therapy, and then some don’t. It just depends on the refractoriness of the disease you’re dealing with.

WESTIN: Since you have the personal experience with CAR T-cell therapy, is there a group, or a type of patient, that you would not want to take to CAR T-cell therapy? Is there a red flag for a situation when you would say CAR T cell is not a good idea?

OBI-ANYADIKE: I think, for the most part, even your 80- to 82-year-old patients do very well with CAR T-cell therapy versus SCT, unless you have a patient with a severe chronic disease—maybe on dialysis—or you have a patient that has a history of stroke, and/or neurological deficit. But, for the most part, it’s pretty well tolerated, other than getting them the lymphodepletion chemotherapy, and then infusion, and then supportive care as they recover from the therapy.

WESTIN: I agree. In our practice at MD Anderson, we take a lot of patients who are borderline candidates for aggressive therapies like SCT to CAR T-cell therapy. I think our eldest person that I’m aware of is 89 years old, but a very fit 89-year-old, not somebody who’s bedbound and had a heart attack last week. These are relatively fit patients for their age, and they can tolerate it well. They don’t always respond to the CAR T cells, of course, but there is at least intention to treat there. But it’s difficult. Sometimes patients that have medical comorbidities; as Dr Lee mentioned, performance status can sometimes be a rate-limiting step. Dr Obi-Anyadike said dialysis it can be a problem. So, certainly there’s reasons why we may not be able to go for CAR T cell therapy.