Expert Discusses CD19 CAR T-Cell Therapy in B-Cell ALL

Eric L. Smith, MD, PhD

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated responses in various hematologic malignancies, particularly B-cell acute lymphoblastic leukemia (ALL).

This population historically has a poor prognosis, but there have been some promising initial high response rates to CD19 CAR T-cell therapy.

In a study evaluating the survival of adult patients with B-cell ALL after CD19 CAR T-cell therapy, investigators infused patients with autologous T cells expressing the 19-28z CAR following conditioning chemotherapy.

Results showed an overall complete remission (CR) rate of 85% and a minimal residual disease CR rate of 67%. The median overall survival was 12.9 months (95% CI, 8.7-23.4).

Investigators found that the durability of 19-28z CAR T-cell mediated remissions and survival positively correlated to a low disease burden. Additionally, allogeneic transplant did not appear to effect outcomes. The researchers concluded their findings support early use of CD19 CAR T-cell therapy in relapsed B-cell ALL.

OncLive: Could you please provide an overview of this study?

In an interview with OncLive at the 2017 European Hematology Association Congress, Eric Smith, MD, PhD, medical oncologist, Memorial Sloan Kettering Cancer Center, discussed the response to CD19 CAR T-cell therapy in B-cell ALL.Smith: We, like other institutions, take a patient’s own T cells and then we engineer into those T cells a gene that on the outside has an antibody fragment that attracts the T cell to the CD19 molecule. Outside the T cell there are stimulatory signals that cause the T cell to both kill and also, equally important, to divide.

The study was first reported back in 2013, and at that time we reported on the first 5 patients. Today I am honored to be able to report on the completion of the study where we treated 53 patients with relapsed/refractory adult B-cell ALL. Historically, these patients have an incredibly poor prognosis, with the 5-year survival in the single digits in older patients and patients who have relapsed more than twice have worse survival.

What is the significance about the results of this study?

Considering the positive results that we’ve seen with this therapy, what are the next steps?

On the study, we treated patients both with minimal residual disease as well patients with blasts counts as high as 97%. We see a CR rate of 85%, with minimal residual disease—negative CR rate of 67%.This is the first study that was reported in adults and these long-term outcomes really show that this is something that is viable for patients. The first cellular therapy products will be approved soon, which is very exciting for patients in ALL, non-Hodgkin lymphoma, and myeloma—where these products are being tested. Significantly, in this study, now that we have the long-term data, we can see that patients who had minimal disease at baseline—when they got the CAR T cells they actually did much better in terms of durability of response. This is significant because it suggests that we should make every attempt to bring this therapy into earlier disease settings when patients have less disease. There are many other studies going on now compared to when we started; it will be great to see which CAR design is the winner. But the really essential thing will be bringing this therapy earlier in the disease setting, potentially in CR1 for maximum disease control benefit.

What challenges still exist in ALL?

This therapy is a viable option that will soon be available at a wide range of centers, and certainly for patients with ALL—even if they are eligible for studies for consolidation in CR1. This should be an option that is strongly looked into, not only in ALL but also in non-Hodgkin lymphoma and myeloma.I think getting patients down to a low disease burden once they do relapse is essential. That really gives the patients the best chance to respond well to this therapy and for a long time.

What other developments with CAR T-cell therapy are you excited about?

The other pressing question is the role of allogeneic transplant after CAR T-cell therapy. In our study, regardless if patients went on to allogeneic transplant or not, their outcomes were very similar, even after controlling for disease burden. The cellular therapy trials in multiple myeloma are extremely exciting. At this year’s European Hematology Association congress, encouraging data was presented by Bluebird Bio and the Chinese company Legend Biotech Co.

We have a trial based on my work that is open at Sloan Kettering, and we are excited to enroll patients there, as well.