Transcript
Hi, my name is Premal Lulla. I'm one of the bone marrow transplant attendings here at Baylor College of Medicine. I'm an assistant professor of medicine.
Today, I will discuss with you our recently published paper in the Journal of Clinical Oncology on using nonengineered T-cells to treat HL and NHL.
We know for a while now that cell therapies are effective against lymphoma. Indeed, there are now several FDA approved engineered T-cell products to treat lymphomas specifically CD19-positive lymphomas.
What we wanted to achieve with this study was to target multiple targets, at the same time express the lymphoma cell. We know that CD19 targeting can lead to antigen negative losses, and we wanted to overcome that by targeting multiple antigens simultaneously.
Therefore, we chose to use a platform of nonengineered T-cells where we can train those T-cells to target multiple different antigens through a sort of in-vitro vaccination approach, where we stimulate these cells against 5 target antigens. These five targets are PRAME, NY-ESO-1, SURVIVIN, MAGEA4, and SSX2.
Once we make these products, we infuse these to patients in 2 arms, 1 of those patients who are at higher risk for relapse. Then, another arm of patients where we gave cells to treat patients who failed several prior lines of therapies.
Since these antigens are not dependent on a subtype of lymphoma, they are expressed by virtually all subtypes of lymphomas. We opened the trial for basically anyone with the diagnosis of lymphoma who has a higher risk for relapse or who has relapsed after many lines of therapy.
The purpose of the study was to establish safety of targeting multiple antigens. We had a dose escalation schema. Even before that, the FDA insisted we do an antigen-escalation schema to demonstrate that by targeting each individual antigen, we're not going to cause them untoward toxicity.
We did 1 antigen targeted T-cell product, followed by 2, followed by 3, all the way up to 5. We relayed patients like that in the run-in phase. The summary is, by targeting 5 antigens, we didn't cause any untoward toxicity signals. It was safe.
We proceeded to the dose-escalation phase, which was completed and presented in the paper. We went from a dose of 5 million cells per meter squared, given as 2 separate infusions, 2 weeks apart, to a total dose 20 million cells per meter square given as 2 infusions 2 weeks apart. We saw no infusion related grade 3 or higher toxicities on the entire trial.
We enrolled a total of 32 patients who received the T-cell products across both the antigen and dose-escalation phases. Of these 32 patients, we had about 17 patients who we gave cells to prevent relapse. These were patients who were already in remission, but had previously demonstrated the capacity to fail chemotherapy or radiation approaches, and so were at a high risk for relapse.
Then, we also gave cells to those patients who had active disease at the time of infusion, meaning that they have failed a median of 2 to 3 prior lines of therapy for their lymphomas. There were 15 of such patients.
The most interesting observations after safety came from the cohort of patients who had active lymphoma. There, we were very pleased to see that across all different lymphoma subtypes with subclinical responses.
In fact, we saw some complete responses were durable. In total, we had 6 complete responders in the active disease scored out of 15 enrolled patients. This was seen in T-cell lymphoma patients, HL patients, as well as NHL patients. The paper shows the outcomes in each different subtype of lymphomas.
The good news is these complete responders were durable. None of the 6 patients who had a complete response subsequently relapsed. This got us very excited for moving this to the next phase of clinical testing.
Now that we've established safety of targeting 5 antigens at a dose of 20 million cells/m2, our next steps are 2-fold. One, that we want to verify this in a larger trial efficacy based, multi-center registry-based trial. That's now going to proceed through a company partnership.
The second is to build upon what we have presented here to improve our response rates.
To that end, we have begun a trial here that combines this product with the hypomethylating agent, known as guadecitabine, which is not a traditional antilymphoma agent, but might upregulate some of these targeted antigens and prevent antigen negative loss.
With that, I'd like to end. Thank you for your time, for listening to us. Hopefully, you get a moment to read our paper.
