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ASCO 2026 | Insights into a study on Mediterranean CD19 genetic variations & CAR-T efficacy
Osama Alsmadi, PhD, King Hussein Cancer Center, Amman, Jordan, discusses findings from a study evaluating the effects of Mediterranean CD19 genetic variants on the efficacy of CAR T-cell therapy. Dr Alsmadi highlights that a key residue at amino acid position 174, prevalent in this population, has been observed to reduce monoclonal antibody affinity in CAR T-cell therapies, potentially contributing to relapse following treatment. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
Well, this has been a project triggered by just the fact that we have some lack of genomic data represented in the global setting. And we wanted to look at the CAR T-cell therapy and how it is related in the genomic perspective. So we looked at some near to 100 exome data from the region, and we focused on the CD19 polymorphism. And we have come across, in fact, one very important key residue, the amino acid number 174 in the CD19...
Well, this has been a project triggered by just the fact that we have some lack of genomic data represented in the global setting. And we wanted to look at the CAR T-cell therapy and how it is related in the genomic perspective. So we looked at some near to 100 exome data from the region, and we focused on the CD19 polymorphism. And we have come across, in fact, one very important key residue, the amino acid number 174 in the CD19. And this happened to be a key player in the interaction with the monoclonal antibody that most of the FDA-approved CAR T-cell therapies are using. And there are some, in fact, true data suggesting that if this variant is changed from leucine to valine, this will, in fact, lowering the affinity of the monoclonal antibody and also some small number of clinical information where they have looked at people with this mutation in the setting of somatic as opposed to germline. And they have found, in fact, they have relapsed after some months post-transplantation. So we really wanted to look at our regional data. Fortunately, there is some real-world data existing now. And in Saudi Arabia, they have so far, in fact, managed to transplant about 200 patients with CAR-T cell therapy using these CAR-Ts manufactured. And the initial data, which is not long-term, near a year follow-up, it’s in fact suggesting there’s some relapse. About 50% are going to complete remission. So we are wondering if this genetic variation that is predominant in the region with the homozygosity approaching 65% for the variant. And this is really raising concern, hypothetically speaking. But we have the data suggesting maybe there is a relationship, yet we have to have stronger scientific evidence. And for that, we are really hoping, you know, we have some research, future research that can be triggered. And maybe our voice will go to the pharmas to really also hear our message and look into prospective studies where this will be taken into account. And the population there, in fact, offers an opportunity for doing this kind of research and collaboration. This is what we’re really hoping to achieve based on our findings.
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