Irena Tan, MD, Stanford Cancer Institute, Stanford, CA, discusses findings from a study evaluating the longitudinal impact of CAR-T therapy on patients’ quality of life, including patient-reported cognitive function and performance-based cognition.

These findings were presented at the 2021 ASH Annual Meeting.

Transcript

Hello, everyone. My name is Irena Tan. I'm a hematology-oncology fellow at Stanford University. I've been working with my coprincipal investigators, Dr Surbhi Sidana and Dr Lori Muffly, on this study that we recently submitted to ASH.

Our abstract is entitled, “Do PROs Tell the Whole Story? Differential Outcomes Based on Patient-Reported Outcomes Versus Performance-Based Metrics on Cognition for Patients Receiving CAR T-Cell Therapy. I'll be pleased to talk briefly about it in this video.

As many people know, there's been a lot of excitement about the wave of new therapies coming down the pipeline for a variety of hem malignancies. One of which the most exciting has been the advent of CAR T-cell therapy.

We're beginning to recognize the unique side effects that come alongside this therapy, such as cytokine release syndrome or neurotoxicity. Our group has always been very interested on the patient experience. What motivated us is the fact that so far, we have a fairly limited understanding of the patient experience with this pretty novel therapy, especially their experience over time.

What we are using to measure the patient experience is largely based on patient-reported outcomes or PROs. The whole field is coming to understand that this may be the most accurate way of capturing how a patient really is doing. Not only is this important in understanding whether or not to use a therapy but hopefully, in also how to use it.

Our patient population for this study has been any patient undergoing CAR-T therapy, regardless of their diagnosis, either at our site at Stanford or at MCW, the Medical College of Wisconsin, our collaborator site. After enrollment, they undergo a series of PRO assessments.

We designed this study with the primary intention of measuring feasibility of the specific PRO instruments that we're using as they are all highly validated, but some of them are completely new to this setting. We're also lucky to be able to also garner data from the PRO instruments that we are using.

We're additionally performing qualitative assessments using patient interviews, which is something that prior to this study, we have very little within the CAR T-cell patient population.

We've been using the promise tool, a widely used health-related quality of life instrument, as well as the NIH neurocognitive toolbox, which is a fairly in-depth performance-based assessment of neurocognition.

Separately, which is also being reported in an ASH oral this year, we've been assessing financial toxicity using a specific financial toxicity PRO instrument. Over the course of a year, patients fill out these instruments or undergo toolbox testing with one of the study members at pre-designated time points, including frequent promise assessments upfront in the month after CAR T-cell therapy. We're hoping to overall enroll 50 patients between the 2 sites. At this point, we're getting pretty close to filling our enrollment.

Our current ASH abstract reports on the interim data that we had at about halfway through enrollment.

First of all, we did find it was feasible. All instruments, including the toolbox, were captured in more than 60% of participants across time points, but more interesting, of course, our early data from the instruments.

For example, we're finding that start out at similar to the United States population baseline for most different physical-emotional domains, and that there is a worsening of fatigue of pain interference and physical function during the month immediately after CAR-T. This all improves back to baseline or even arguably better than their baseline after 3 months.

Similarly, anxiety and the ability to participate in social roles also dips immediately after CAR-T but also is improved back to baseline by month 3. In essence, quality of life so far seems to be longitudinally sustained with CAR T-cell therapy.

In our neurocognitive assessments, using the toolbox, while we still only have a limited number available, initially, we actually couldn't implement it because of COVID restrictions, and this toolbox requires an in-person assessment. Since implementation, we've been able to have pretty good completion rates.

Preliminarily, we're seeing suggestions that cognition may objectively worsen from baseline to a month after CAR-T, which is in contrast to the patient-reported subjective cognition, which has remained completely stable. Perhaps when it comes to cognition, a patient report isn't quite as sensitive at detecting minor changes as an objective measurement.

As for the financial toxicity portion of all this, also interesting, but you'll have to watch our ASH oral for more detail so we don't spoil it for our colleagues.

Ultimately, what are the takeaways? We need to learn more about how patients are experiencing this treatment, CAR T-cell therapy, that's becoming an increasingly important part of treating multiple different diseases.

Ours is the first longitudinal study of a variety of patient-reported outcomes in this patient population some of which have never been assessed. This kind of study does appear to be feasible in spite of the novelty of these instruments.

So far, health-related quality of life appears to be maintained in the long run, but cognition, which is an area of increasing interest because of the neurotoxicity seen with a small but not insignificant number of patients, this remains an open question. Our study seems to suggest that patient reports of cognition may not be as sensitive as we hope.

Tan I, Cusatis R, Crawford E, et al. Do PROs Tell the Whole Story? Differential Outcomes Based on Patient-Reported Outcomes (PROs) Versus Performance-Based Metrics (PBM) on Cognition for Patients Receiving Chimeric Antigen Receptor (CAR)-T Cell Therapy. Presented at the ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA and Virtual. Abstract 3043.