CART Immunotherapy could Give Earlier for Better Outcome in Pediatric ALL--Dr. Stephan A. Grupp's Interview at ASCO 2015

Dr. Stephan A. Grupp, MD PhD Professor

Director of Translational Research

Center for Childhood Cancer Research at The Children's Hospital of Philadelphia

Medical Director, Stem Cell Laboratory

Chair, Stem Cell Transplant Discipline, National Children's Oncology Group

Source: Oncology Frontier《肿瘤瞭望》

Oncology Frontier《肿瘤瞭望》：What’s the novel agents developed for Children and adolescents with refractory/relapsed ALL？
 

Dr. Grupp: What we are talking about at this conference is CAR (chimeric antigen receptor) T-cell therapy--which is engineered T-cell therapy.

T-cells are genetically engineered with a chimeric antigen receptor. This receptor attacks CD19 which is found on almost all B-cell malignancies and almost all ALL. It's a really good target.

These T-cells are engineered using a virus. They are collected from each patient and given back to that patient and those cells then grow in the body and expand enormously ultimately controlling the disease.

What we have seen is that 94% of patients that we have treated with refractory or relapsed ALL have gone into complete remission. We are very excited about that. Three-quarters of these patients remain in remission at six months and 81% of them are still alive. So the data now have some longer term follow-up.

The first patient we treated three years ago is still in remission, and most of these patients have not required any further therapy such as bone marrow transplant.

Can you summarize some humoral and cellular immunotherapy strategies which found to be effective, safe, and well tolerated?
 

Dr. Grupp: The area of immunotherapy for ALL has really gotten very exciting.

There are certainly antibody-mediated therapies out there. Recently approved in the United States is blinatumomab--which is a bispecific T-cell engaging antibody that is also very active (although not as active as CAR T-cells). It is easier to access, though, because it is an off the shelf drug where you don't need to make cells from the patient.

Other treatments that are being developed include moxetumomab and inotuzumab, which are conjugate antibodies with immunotoxins which then attack the antigen CD22. There have been excellent responses seen with both of those.

In general, I would say the antibody products are better tolerated than CAR T-cells, where the toxicities are higher, but CAR toxicities are manageable and we are seeing much higher response rates compared to antibody products.

With an overall decrease in toxicities experienced by patients, how to determine when in the course of treatment with humoral and cellular therapy will have the safest and optimal effect in ALL？

Dr. Grupp: Right now we are treating very advanced stage patients and we are learning in the CAR T-cell field that in patients with higher tumor burden, we can still get excellent control of the disease but there is higher toxicity.

With the antibodies, the control of disease with very high disease burdens is not as good as with CAR T-cell. So if we can move patients into treatment earlier, I think we will have better toxicity outcomes with the CAR T-cells and better efficacy outcomes compared to the various antibodies.

I do believe that in pediatric ALL, the challenge is to define high-risk patients, which we can do genetically or with minimal residual disease testing.

In adults--the outcomes are not as good and it will probably be easier to deploy these therapies earlier.

Reference:

[ASCO2015]CAR-T细胞在儿童白血病中的应用--Stephan A. Grupp教授访谈 2015/6/5 Video 肿瘤瞭望