Bijal J. Shah, MD
In March 2017, tisagenlecleucel-T (CTL019) became the first chimeric antigen receptor (CAR) T-cell therapy to enter regulatory review when the FDA granted the treatment a priority review for use as a treatment for pediatric and young adult patients with relapsed and refractory B-cell acute lymphoblastic leukemia (ALL).
The FDA’s subsequently Oncologic Drugs Advisory Committee (ODAC) subsequently scheduled a public hearing for July 12, 2017, to discuss the biologics license application for tisagenlecleucel-T in ALL.
At the recent 2017 OncLive®
State of the Science SummitTM
on Hematologic Malignancies, Bijal J. Shah, MD, discussed the success of CAR T-cell therapy in ALL.
“What CAR T-cell therapy is generating in terms of the likelihood of remissions, durability of remissions, and improvements of survival are beyond what we have seen with other agents that have been newly approved in the same space. This gives us a lot of reason for optimism moving forward,” explains Shah.
In an interview with OncLive, Shah discussed the significant impact CAR T-cell therapy can have on the treatment landscape for patients with ALL.
OncLive: Can you provide an overview of your presentation at this meeting?
I wanted to summarize the work that’s been done across the clinical trials in adult ALL. We will hopefully see our first approval in pediatric ALL sometime this year since the data has been submitted to the FDA and is currently under review.
On the adult side, we’re following closely behind. I’ve been heavily involved in the Kite CAR T-cell trial. There are other trials, such as Juno, that have been working very closely in this space, as well. Novartis will likely also be entering this space in the near future.
We’re going to have these cellular therapies for ALL, which is very exciting. What CAR T-cell therapy is generating in terms of the likelihood of remissions, durability of remissions, and improvements of survival are beyond what we have seen with other agents that have been newly approved in the same space. This gives us a lot of reason for optimism moving forward.
Are there any reasons as to why this type of therapy has received greater attention in ALL than in other malignancies?
It's because of the poor outcomes that we otherwise observe in patients with relapsed leukemia. We know for patients in first relapse from the MRC ECOG data that their long-term survival is in the range of 3% to 7% at 5 years.
We can improve that to as high as 20% with a transplant for those that are able to get a remission. We haven't improved much beyond that.
We are beginning to improve results further with other novel therapies in this space, but we are still plateauing at 20% long-term survival.
Our hope with CAR T-cell therapy is that we can do better. We already have a sense from the earlier studies that we're going to increase progression-free survival. However, we don’t yet know to what extent that will translate into both a short- and long-term survival benefit or the role of allogeneic transplant.
Do we know which patients are most likely to receive this type of therapy or are able to tolerate it better?
On the adult side, we have not tried to limit participation. I can say this for both the Memorial Sloan Kettering Cancer Center (MSKCC) study that was done, as well as the ongoing Kite study.
We have standard inclusion and exclusion. For example, patients cannot come on with kidney failure, liver failure, or severe infections. These are standard inclusion and exclusion criteria that are seen across any trial. I don’t think that that is a good reflection of who benefits or who doesn’t, since it’s more for a standard trial.
A better way to think about it is magnitude of benefit. We know from the NCI data, the Fred Hutchinson data, and the MSKCC data, that those who are treated with CAR T-cell therapy who have minimal residual disease (MRD), have much better outcomes.
The data from MSKCC were very pronounced in those regards. The survival for those who underwent a transplant is slightly less but there is going to be more morbidity that comes from a transplant. I don't think anyone will say that a patient with relapsed leukemia should not receive a transplant. However, the magnitude of benefit that was seen in this low-disease burden population is interesting. Again, similar findings were observed at Fred Hutchinson and NCI, when they looked at patients who came in with MRD.
We know that the toxicity is a reflection of T cell expansion and the T cells are going to expand when they encounter that CD19 on the leukemic cells.