Jonathon Cohen, MD, Assistant Professor, Department of Hematology and Medical Oncology, Emory University School of Medicine, Medical Director, Infusion Services, Winship Cancer Institute of Emory University, Atlanta, Georgia, spoke to Oncology Learning Network about a recent trial presented at the ASH Annual Meeting which studies real world results of axicabtagene ciloleucel in B-cell lymphomas.

Transcript

Thank you very much for having me. My name is Dr. Jonathon Cohen. I'm an assistant professor at the Winship Cancer Institute at Emory University in Atlanta.

One of the things that we thought about when we were developing this study was that there were a lot of data that were now coming out evaluating the role of chimeric antigen receptor T-cells, or CAR-T cells on clinical trials, for patients in clinical trials.

In the last year or so, there's been several FDA approvals, especially in diffuse large B-cell lymphoma. There was considerable interest among our co-investigators to try to describe the experience for those patients that are receiving treatment outside the setting of a clinical trial.

In this particular project that was led by Caron Jacobson at the Dana-Farber Cancer Institute, we evaluated the experiences for patients who received axicabtagene ciloleucel, or axi-cel, off of a clinical trial. That is, these are patients that received it based on the FDA indication.

We felt that this type of study was particularly important because we often find that the experience for patients, as well as for physicians that care for patients outside of a clinical trial, is occasionally different than what is experienced for patients that are on the clinical trial.

This is often because patients that qualify for a clinical trial often may have a better performance status, may have fewer comorbidities, and, in general, are able to travel to a select group of centers that are conducting the trial.

Frequently, once a therapy is FDA approved and is available more widely, we see that patients that may or may not have actually qualified for the clinical trial still go on to receive the treatment based on its labeled indication. Occasionally, this can change the experience for the patient and the outcomes.

Our study found that, fortunately, the experience for patients that are treated off study with commercially available axi-cel is typically similar to those patients that were treated on study. In this particular cohort, we initially identified 104 patients, of which 13 ultimately never received their infusion. This was due to either progressive disease, infection, or occasionally a failure of manufacturing.

This is a relatively low rate of patients not ultimately moving on to infusion, but does highlight some of the challenges with managing patients with relapsed aggressive lymphoma in that, occasionally, they can develop complications from their treatment or may have a disease that is progressing so quickly that they aren't able to receive therapy.

What we did find among this cohort was that the response rate was at 71 percent. When we included those patients who ultimately didn't receive therapy but for whom manufacturing was attempted, which was the full cohort, the response rate was 62 percent.

While this is a little bit lower than what has been reported in the ZUMA-1 clinical trial, it still demonstrates that a large number of patients are benefiting from this therapy. Of note, the complete response rate was 44 percent. We feel that these are likely the patients that are the most likely to benefit in the long run.

Again, we did see that there was a considerable number of patients that experienced a complete remission. Fortunately, a large number of these patients remained in remission at six months.

In addition, we did identify several toxicities which are known to occur in patients that receive CAR-T infusions. Most notably, we saw cytokine release syndrome in 94 percent of patients and neurotoxicity in 76 percent of patients.

In the majority of these cases, however, the toxicity was low grade. Grade three plus toxicity, which is more of the life-threatening variety that we worry about and that can sometimes result in patients having to be admitted to the intensive care unit, did occur.

We saw that the rate of grade three plus cytokine release syndrome was 16 percent and that the rate or grade three plus neurotoxicity was 39 percent.

These are both values that are roughly comparable to what's been seen in the clinical trials and, again, reflects the fact that, at least within this cohort of patients, that the outcomes were relatively similar to what's been described in the clinical trial.

I would point out that patients that received therapy were those that met the FDA indication for relapsed refractory diffuse large B-cell lymphoma. At the current time in the United States there is not an opportunity for off-label usage of this therapy. We can feel comfortable that these were all patients that met the labeled indication and that would have potentially been candidates for the ZUMA-1 clinical trial.

This finding has a number of clinical implications, most notably the fact that we can feel comfortable that appropriately selected patients that are managed at specialized centers can safely receive CAR-T infusion and that the findings from the clinical trial can likely be extrapolated to the real-world setting in this particular instance.

I think that some of these similarities are likely due to the fact that axi-cel is still only available at a select number of centers that have experience with cell therapy. Centers must undergo a rigorous start up process to make sure that they are able to manage patients that are receiving CAR-T therapy.

It appears that this approach has been very successful in that we are continuing to see patients that receive therapy, that have their toxicities managed appropriately, and that are achieving long-term remission.

I would encourage anybody who is potentially a candidate for this type of therapy to seek out one of these centers because it does appear that with longer follow up and with additional patients treated, we are continuing to see successes with this therapy.

Since ASH has completed, we've had the opportunity to communicate amongst ourselves to discuss where we should go next with these findings. One other area of interest is that there is a second real world experience that was presented at ASH that was led by Loretta Nastoupil from MD Anderson.

Now that we have these two large cohorts of patients, there's a lot of interest in trying to better identify those patients that are likely to be successful versus those that are more likely to relapse and, potentially, to also learn a little bit more about clinical predictors of toxicity.

We're still debating the next steps for this particular project. I think there's a lot that we could do with such a rich data source that we have.

One of the aspects of this real-world study that is still lacking is the long-term follow up. While we are starting to have some patients that have been followed for several years on clinical trials, many of these real-world patients only have follow up of a few months to, potentially, up to a year or so based on the fact that the FDA approval is still so recent.

One area of continued interest is learning more about the long-term impact of these therapies, both from the standpoint of disease control, as well as long-term toxicities that may arise. I think, in future years, we hope to continue to use this cohort to identify any long-term side effects or complications that develop with this therapy.