As a shining new star in the medical field, CAR-T cell therapy, while significantly effective, is filled with unknowns much like Pandora's Box. From successful treatment to long-term monitoring, every step requires meticulous planning. Recently, at the 12th Lu Daopei Hematology Academic Forum, Hematology Frontier had the honor of inviting Dr. Shahrukh Hashmi from the Mayo Clinic Comprehensive Cancer Center to share in-depth insights on the optimization and practical experience of long-term monitoring strategies following CAR-T therapy.

Hematology Frontier：The metaphor of “Pandora’s box” you mentioned seems to imply the unknown and potential risks thatCAR-Tcell therapy may bring. How do you understand this metaphor and how do you address these challenges in your practice?

Dr. Shahrukh Hashmi：Pandora’s box. When you open it, you have no idea what’s coming up. That is true for anything which is very, significantly curative, but also a brand new therapy and a complex therapy like CAR-T cells. And a few decades ago, a bone marrow transplant. I’ll give you an example of a childbirth. The pregnancy of 9 months in humans is a laborious task for a female and kudos to all the women in the world carrying the baby for 9 months. When the baby is born, the question is, that’s when another story starts a long term story. What next?Now who’s gonna follow the baby from childbirth till the teenage? That’s gonna be the fundamental question for any new therapy and a complex therapy that comes in medical world as well. Not that we cured a patient with leukemia lymphoma, but then what who is going to monitor those patients for the knowns and unknown complications in long term. So that’s where the analogy of Pandora’s box comes in.

Hematology Frontier：CAR-T cell therapy has shown remarkable efficacy in hematologic malignancies, yet long-term complications remain a focal point. How do you perceive the improvement in long-term survival rates postCAR-Ttherapy and the management of related complications?

Dr. Shahrukh Hashmi：The the fundamental principle of assessing the complications and preventing them in a patient after a CAR-T cell is to have an organized, systematic fashion, a clinic called survivorship clinic for these survivors who got a CAR-T cell so that we can monitor the known and the unknown effects of the CAR-T cells very carefully, whether it be new cancers to have an eye on those to screen them, or the heart complications or the brain complications or anything else, or the cancer itself may be coming back.

We have to monitor that and those kind of clinics called long term follow up clinic, or survivorship clinics are needed much more today than ever. Because people from all over the world are travelling to few centres, which can do CAR-T cell, for example, from hundreds of thousands of cities in China. They go to a few selected centers to get CAR-T cells for their leukemia, lymphomas or myeloma. When they go back, the first year follow up is great, but we need to have mechanisms to follow them up year after year, after year, after year.

And this is true even for the young kids who get the CAR-T cells, because what’s gonna happen when they’re going to have babies who’s going to actually assess the risk of them having normal kids in the future, who’s gonna assess these patients from the age of 15 all the way up to the 50. It’s our responsibility. The way I envision this is having a very organized CAR-T survivorship program in the hospitals which perform CAR-T cells.

Hematology Frontier：what new strategies or methods have been proposed to predict and reduce the risk of long-term complications followingCAR-Ttherapy?

Dr. Shahrukh Hashmi：Fortunately, most of the continents where we’re doing CAR-T cells, we’re forming workhouse registries. We’ve learned from bone marrow transplant fields that these registries will give us a clue about the complications and late effects that happen after the CAR-T cells.

Now, once you’ve got mega data from them, for example, 10 year data of the CAR-T cell of a group of patients, we would hope that the international registries will merge with each other so that we have more data.

And then we be able to better predict by artificial Intelligence methodologies, machine learning, methodologies, that what are the individualized risks of patients based on the exposures, which is the chemotherapy, the CAR-T cells that they had in the past? To predict what kind of complication they may have for this cardiovascular, which is a heart or brain complications or new cancer development. It will come from those precision medicine models based on machine learning, deep learning methodologies, which is AI once we have the mega data simulated, which we’re accumulating now.