John P. Leonard, MD: Nathan, in a minute I'm going to ask you about the long-term follow-up and reality for older patients but I want to ask Matt quickly about a couple of abstracts presented at ASCO [American Society of Clinical Oncology]that are fairly preliminary but intriguing at least. One abstract addresses re-treating patients and the other addresses moving towards a second line. How do you see all of that emerging?
Matthew Lunning, DO: If there is a second product that's made and a patient relapses at 12 months and had a CR [complete response], I would determine if they're an allo [allogenic stem cell transplant] candidate to know that you could go to allo and they won’t have high-grade toxicity. The data shows for patients that have a response without much toxicity, CAR T cells, compared with chemotherapy in a double- or triple-refractory patient, have good odds to get you into remission.
I would try to consolidate and use the CAR-T cell as a bridge to a different form of cellular therapy, allogenic stem cell transplant – which we have been using for much longer than CAR-T cell therapy –if they are able to. In a person who I can't bridge to something, I'd be looking for a CAR-T cell plus a novel combination or not doing it at all if it was too cost prohibitive.
John P. Leonard, MD: Kami, what do you think about second-line therapy? There was data presented at ASCO suggesting that the PR [partial response] patients still do well with an auto transplant. We have randomized trials looking at second line CAR T versus chemotherapy and transplant. What are your thoughts on that at this point? Is there a patient in practice, assuming you have access, where you made choices in that? Or do you pretty much give everybody the second-line chemotherapy at this point?
Kami Maddocks, MD: At this point, if there was a trial with 1 of the products and now there's a second trial looking at those early progressives or those patients who were refractory, and if I can get them on the trial for a potential for the CAR T therapy as opposed to just giving them chemotherapy, that's great. Otherwise, I will give them just chemotherapy. We are going to see a benefit to giving CAR T to refractory patients as opposed to just giving them platinum salvage and auto transplant.
As far as a patient's response to chemotherapy, that depends on how you define the PR. If somebody gets only a partial response and still has a ton of disease versus if somebody hasn’t achieved a CR but they have very minimal disease activity, there is probably more benefit to proceeding to transplant in that second population. I think the one area of interest is patients who are not candidates for auto transplant but maybe they are candidate for CAR T. There is no real definition the candidacy for CAR T, but it is typically somebody with at least reasonable performance status, good cardiac function or lung function. In that group of patients, there was an ASCO abstract that showed being able to infuse CAR T and that group of patients who were considered transit candidates for transplant is a great group to target for this therapy also.
John P. Leonard, MD: Nathan, [The University of Texas] MD Anderson [Cancer Center] has been involved, as has Ohio State University Medical Center and University of Nebraska Medical Center with some of the earlier trials. What's your experience with the long-term follow-up of patients treated with CAR T in relation to data presented at ASCO? I tend to tell people it's 3 thirds; a third of people have a long remission, a third have a short remission and transient benefit, and a third get 0. Is that what you tell people or how do you look at it?
Nathan H. Fowler, MD: We've seen long-term follow-up along with real-life experience with two of the big CAR T cell products. You hit the nail on the head. Matt's analogy of apples to apples to apples applies here. Although the response rates and the CR rates are a little different, the long-term durable remissions across all 3 of these products is in the mid-30s to the low 40s with most of these patients. That tends to be confirmed with not only long-term follow-up but the real-life experience with a lot of these trials. We've also seen the outcome of elderly patients. There was an abstract in this recent ASCO suggesting that elderly patients also do fairly well with CAR T cells, slightly less well but still you're looking at 20%, 30% of patients that are probably going to be cured in the elderly population.
Transcript Edited for Clarity