At 3 years of follow-up, CD22-directed CAR T-cell therapy continued to show durable remissions for patients with large B-cell lymphomas which had previously relapsed after CD19-directed CAR T-cell therapy.

Anne Marijn Kramer, MD, PhD, Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA presented these results at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, California.

“CAR22 provides durable remissions and long-term survival in CAR19-progressing LBCL patients,” Kramer and colleagues explained. “Late progression or lymphoma-specific death was uncommon, suggesting a curative potential for these patients.”

Transcript:

My name is Anne Kramer. I am a postdoctoral fellow at Stanford University, and our abstract covers the extended follow-up of a trial run at Stanford in which we investigated a CD22 targeting CAR in patients with large B-cell lymphoma and who had progressed after receiving CD19-targeted CAR T-cell therapy. 

We have already published that the overall response rate was 68%, with a complete response rate of 53%. Now at the presentation of this abstract, we have reached a median follow-up of over 36 months in a total cohort. What we show in the abstract is that these responses, so those patients who achieve a complete response are actually durable. Of our 20 patients who achieved the complete response, only 4 have relapsed, 2 being relatively soon after infusion at three and six months and two at around 2 years after infusion.
In terms of durability of the responses, we see that those who achieve a complete response, those responses are actually very durable, and the estimated 3-year progression-free survival for the patient since CR (complete remission) is 58%. 

More importantly, if we look at overall survival, the contemporaneous median overall survival of these patients after relapsing to CAR19 at the time was around 6 months. We now see that at our recommended phase 2 dose, the median overall survival for the total cohort is 25.7 months, so a stark improvement, but even more so for those patients who achieve a complete response, the estimated 3-year overall survival is 74%.

This truly shows the curative potential of this construct I believe in these patients who previously had very little options in terms of follow-up therapy following CAR19 progression. 
None of our patients in CR have died of lymphoma. In terms of long-term toxicity, we do, however, see that this cohort has been heavily pretreated. So, the median lines of prior therapy was 4, which I think is reflected in the prevalence of secondary treatment-related myeloid neoplasms. So, 4 patients in our cohort have developed the treatment-related myeloid neoplasm approximately 30 months after infusion. They all have been heavily pretreated, so this certainly warrants further follow-up of all of our patients to better understand this and identify those patients at risk.

None of our patients in CR have died of their lymphoma, which is really encouraging. And in terms of prolonged cytopenia, we saw that at the one- and two-year milestones after infusion, cytopenia actually seemed to resolve with a few exceptions of neutropenia that were likely in the context of these myeloid neoplasms that were developing. In terms of infections after transfusion, we saw from six months post-infusion we did have a few cases of infections requiring hospitalization, and this included four cases of respiratory viral infections and one of neutropenic fever, which was actually very short-lived.

But overall, we see that those patients that achieve a durable remission to this CAR do very well. As I said, you know, we reached a median follow-up of three years and believe that given the favorable toxicity profile of this CAR, this would justify studying this specific construct at earlier lines of therapy. Lastly, there is a phase 2 trial ongoing still, so this was a phase 1 trial with a relatively small cohort, but hopefully, the phase 2 trial will give us more insights into this construct, and we're also at Stanford investigating this same construct for other lymphoma subtypes.
 

Source:

Kramer AM, Baird JH, Srinagesh H, et al. CD22-Directed CAR T-Cell Therapy for Large B-Cell Lymphomas Progressing after CD19-Directed CAR T-Cell Therapy: Continued Durable Remissions at 3-Year Follow-up. Presented at the 66th ASH Annual Meeting & Exposition; December 7-10, 2024; San Diego, California. Abstract 69.