ASH 2022 | Phase I study of CD22-targeted CAR-T therapy in patients with CD19-negative B-ALL
Regina Myers, MD, Children’s Hospital of Philadelphia, Philadelphia, PA discusses the results of a Phase I clinical trial (NCT02650414) using a CD22-targeted CAR-T product in children and young adults with B-cell acute lymphoblastic leukemia (B-ALL) who have relapsed with CD19 antigen loss after CD19-targeted CAR-T therapy. The results demonstrated remissions in 77% of patients, with no reports of serious adverse effects. Dr Myers notes that patients who received a consolidative transplant following this therapy experienced lower relapse rates. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.
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Transcript (edited for clarity)
We’re presenting here the results of our Phase I trial of a CD22 targeted CAR-T cell product for a population of patients with very highly refractory CD19-negative relapse following prior CD19 directed therapy. So we know that these patients are extremely high-risk. Patients who relapse following CAR19 with CD19 antigen loss, have extremely poor survival with a median overall survival of less than 10 months from the time of their relapse...
We’re presenting here the results of our Phase I trial of a CD22 targeted CAR-T cell product for a population of patients with very highly refractory CD19-negative relapse following prior CD19 directed therapy. So we know that these patients are extremely high-risk. Patients who relapse following CAR19 with CD19 antigen loss, have extremely poor survival with a median overall survival of less than 10 months from the time of their relapse. And so there’s really a very urgent need to develop novel therapies for these patients.
So we developed a novel CAR construct termed CART22-65s and administered that in a Phase I trial. We had a total of 20 patients screened, 19, enrolled and 17 ultimately infused. And all 17 of those were valuable for response. And we were really excited to see really high complete response rates. So 77% of patients entered a CR at day 28. And again, these are patients with extremely limited therapeutic options.
Following initial response, however, we do see a lot of patients go on to subsequently relapse, especially if they did not follow CART22 therapy with a consolidative transplant if they were just using CART22 as definitive therapy. Although we do have one patient who did receive CART22 just as definitive therapy and is in a long-term remission from that. But we do have some patients who went on to consolidative transplant who stayed in long-term remissions.
I think the other piece of the study that we were really excited and gratified by was the safety profile. These were patients who, again, really highly refractory and most of them came into CART with very high disease burden, which we know is the number one predictor of having severe toxicity after CAR-T cell products. But despite very high disease burden, we actually, in the initial infusion setting, didn’t see any grade 3 or 4 cytokine release syndrome or ICANS. We only saw grade 1 and 2. And so really a nice tolerable safety profile knowing that this is a potential therapeutic option for patients with really limited therapeutic options.
And then I think the other big takeaway from this is we know, again, seeing some later relapses after that first remission that you get with CART22, it really highlights the need to use CART22 as part of combination therapy, not just on its own. So whether that’s in combination with transplant, like many patients on this study use, or in combination with a CART19 product as a dual-targeted CAR. And that’s where we’re very excited to go to next with this data.
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