ASCO: CAR-T in the Real World

More from this year's ASCO conference.

As has been the case for the last few years, there were a lot of presentations this year on CAR-T. That's not a surprise, and if you've been reading for a while, you know that CAR-T (along with bi-specifics) is one of the treatment types that gets Lymphoma specialists most excited these days. As you probably know, CAR-T describes several specific treatments. All of them work the same way -- a patient has T cells removed from their blood (T cells are a type of immune cell), the T cells are changed in a lab to recognize cancer cells, and then they are put back into the patient to do their job. It can be a very effective treatment, though it comes with some potentially dangerous side effects, and since each treatment is individualized for each patient, it can be very expensive as well.

Two presentations that caught my eye were "real world" studies of CAR-T. A "real world" study means something very specific. When a clinical trial is designed, researchers make up a list of patients who will be included -- a specific disease, specific previous treatments, etc. But they also include a list of "exclusions" -- things like the time since a last treatment, and most importantly, specific comorbidities, or health already existing health problems. This can be controversial, since it excludes a bunch of people who might otherwise benefit from the trial. But the logic makes sense -- if the treatment in the trial might cause heart problems, then one group excluded from the trial might be patients who already have heart problems. That way, if patients in the trial begin the develop issues with heart rhythm, for example, the researchers will be confident that the problems came from the treatment being tested. 

But the other controversy that comes from this practice is that it could give an unrealistic picture of how safe and effective the treatment is. In other words, if a trial involves 500 patients, and none of them have a history of heart problems, then we really don't know how the the treatment will affect the roughly 80 million people in the United States who have some form of heart disease. 

That's where "real world" studies come in. After a treatment has been approved by the FDA, the are no  ore requirements for doing studies. But some researchers will perform "real world" studies, without the kinds of exclusions that happen in a trial. It's a way of collecting information about how a treatment is going outside of a trial -- how effective it actually is, and how safe it actually is.

As I said, there were two "real world" studies of CAR-T this year that involved Follicular Lymphoma patients. The first is "7509: Real-world early outcomes of axicabtagene ciloleucel for relapsed or refractory (R/R) follicular lymphoma (FL)." This one looks at one specific type of CAR-T, known as Axi-cel, or Yescarta. 

The study involved 230 patients who received Axi-cel, including those 92 who would not have been eligible for the ZUMA-5 trial that looked at Relapsed or Refractory FL patients. In the trial, about 94% of the patients had a response to Axi-cel. The study looked at 151 patients who were available for follow-up. The results were very good. The Overall Response Rate was 93% (compared to 94% in the clinical trial), with an 84% Complete Response. The estimated Progression Free Survival at 6 months was 88%, and the Overall Survival at that time was 96%. Safety was good, too, with only 2% of patients having severe Cytokine Release Syndrome (probably the most serious possible side effect), and 13% having severe nerve issues. The PFS and OS were about the same as those in the ZUMA-5 trial, though it was more common for patients who would have been excluded from the trial for health reasons to have more severe side effects.

Overall, then, the "real world" study confirmed that Axi-cel was as effective as it seemed to be in the clinical trial, with some safety issues for patients with more health problems.

The second "real world" presentation at ASCO was called "18896: Real-world duration of hospitalization for CAR-T treatment: U.S. patient experience in multiple hematologic malignancies." It looks at all 6 types of CAR-T that have been approved for blood cancers,and looks specifically at how long patients needed to be hospitalized during the CAR-T treatment process.

The study looked at a total of 212 blood cancer patients, including 47 who were diagnosed with Follicular Lymphoma, who received CAR-T sometime between 2017 and 2022. The researchers found that the median duration of the time spent in the hospital was 12 days. One question they asked was whether or not hospital stay lengths have decreased over time (since doctors are getting much better at identifying side effects early, before they cause severe problems). The answer is that there is a slight decrease -- for patients who had CAR-T between 2017 and 2019, it was 12.3 days, and for patients who received it between 2020 and 2022, it was 11.9 days. 

They also wanted to know if patients who had Cytokine Release Syndrome (remember -- potentially dangerous side effect) ended up with a longer hospital stay. The answer to that question was, again, a slight difference -- 12 days for patients with CRS, and 11 days for those without.

Since all of this information came from a database (rather than studying individual patients), the researchers point out that there needs to be more research into other factors, like the hospital systems themselves, and the details of the patients' individual health issues, to really get a sense of how accurate their research is.

But like the first study, this research shows how important it is to continue to study treatments, even after they have been approved, to see how they actually affect patients in the "real world." 

As for CAR-T, there's no evidence that it isn't as effective as it had already been found to be. And it certainly seems that doctors are getting enough experience with CAR-T patients to identify and treat side effects as soon as they can. CAR-T is certainly here to stay. It will be interesting to see just how many of us end up having it as a part of our treatment in the future.

There are still a few more interesting ASCO presentations to share, but I'm also seeing a whole bunch of non-ASCO stories that you'd probably enjoy. I'll have plenty more to share and comment on soon.