Dual CAR T-Cell Therapy for Leukemia Could Impact Safety, Different Population of Cells

There are several strategic approaches to multi-targeting in acute lymphocytic leukemia (ALL). Whether it is through co-infusion, co-transduction, or dual targeted approaches, there is still deeper follow-up needed to analyze the persistence of these approaches, according to a session presented at the 10th Annual Meeting of the Society of Hematologic Oncology, held in Houston, Texas.

Noelle Frey, MD, University of Pennsylvania in Philadelphia, Pennsylvania, discussed how in patients with relapsed/refractory ALL, remissions occur quickly and are independent of mutations. However, relapses have still been a challenge for most patients without stem cell transplant.

As for dual targeted approaches with chimeric antigen receptors (CARs), Frey said bi-specific, bicistronic, co-transduction, and co-infusion are the most used CARs and highlight the challenge in engineering multi-specific CARs with equivalent potency across targets.

“These dual targeted approaches are still under active investigation as for whether these dual targeted approaches end in dual functionality,” Frey said.

In a phase 1 trial of huCART19 and CART22-65s for adults with relapsed/refractory ALL, the primary endpoints were achieved, which was the frequency and severity of adverse events (AEs). The secondary endpoints were also achieved, which included overall survival and duration of remission. Cytokine release syndrome and neurotoxicity from tocilizumab and corticosteroids led to 2 deaths before day 28, which was seen as a rapidly progressive disease or a treatment-related cause.

At the median follow up of 11.8 months, one patient was seen with molecular recurrence, while 10 had ongoing complete remission/complete remission with incomplete count recovery (CR/CRi).

Frey said that the goal of dual targeting is to minimize the risk of relapse due to antigen modulation and the development of maintaining dual functionality. Although these types of approaches have overall been found safe, different populations of cells and the safety and efficacy of dual CRS/ICANS could impact the patient.

Additionally, Frey anticipates dual episodes of neurotoxicity in the future as some treatments are limited in the ability to complete dual targeting, which is why further analysis is highly recommended in this area of ALL.

REFERENCE

Frey, Noelle. Dual CAR T-Cell for ALL. September 28th, 2022. Accessed October 4, 2022. 10th Annual Meeting of the Society of Hematologic Oncology. Houston, Texas.