Some pediatric sufferers with B-ALL could profit from a novel CAR-T cell remedy, in response to a presentation on the 2024 ASH Annual Assembly.
Kids with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) demonstrated excessive remission charges after remedy with a novel bicistronic CD19/CD22-directed CAR-T cell remedy.
The remedy additionally generated sturdy responses and was proven to be secure amongst these sufferers, together with these with remoted or mixed extramedullary relapsed illness, in response to up to date information from a part 2 trial introduced on the 2024 ASH Annual Assembly.
At a median follow-up of 13.9 months, the one-year event-free survival (EFS) charge was 75.5%, and the one-year total survival (OS) charge was 93.5% amongst sufferers enrolled and handled with bicistronic CD19/CD22-directed CAR-T cell remedy (343 sufferers).
Glossary
Bicistronic CD19/CD22 CAR-T cell remedy: a selected sort of CAR-T cell remedy that targets two proteins on B-cell leukemia cells: CD19 and CD22.
Occasion-free survival (EFS): the size of time after remedy {that a} affected person lives with out the most cancers returning or worsening.
Total survival (OS): the size of time a affected person lives after being identified with most cancers, no matter their illness standing, till demise of any trigger.
Cytokine launch syndrome (CRS): when the physique releases too many cytokines into the bloodstream and overreacts to an an infection or harm. It is a critical situation.
Full remission (CR): when sufferers absolutely reply to remedy, which means they not present indicators or signs of most cancers.
Minimal residual illness negativity: minimal residual illness means a small quantity of most cancers cells could stay within the physique after remedy. Negativity refers to having no traces of most cancers within the physique after remedy.
Following CAR-T cell enlargement, the one-year EFS charges amongst sufferers who underwent bridging bone marrow transplant (38 sufferers) versus those that didn’t (280 sufferers) have been 89.7% versus 76.8%, respectively. The respective one-year OS charges have been 95.8% versus 95.2%.
“After CAR-T cell remedy, we’ve discovered that the one-year EFS [rate] is increased [with] CAR-T cell remedy plus bone marrow transplant than CAR-T cell remedy alone, [although the] one-year OS [rates were] very related between these two [populations],” presenting writer Dr. Hua Zhang, vp and chief scientific officer at SPH Biotherapeutics (HK), Restricted, acknowledged in an oral presentation of the info throughout a digital press briefing.
Most sufferers developed cytokine launch syndrome (CRS); these with lower-grade CRS had higher one-year EFS outcomes than these with higher-grade CRS. Among the many 172 sufferers with grade 1 or 2 (delicate or average) CRS, the one-year EFS charge was 80.9%. The one-year EFS charge for the 145 sufferers with grade 3 or 4 (extreme or life-threatening) CRS was 69.9%.
Within the presentation, Zhang added that “on this examine, we discovered the severity of CRS was not associated to the examine dose vary of infused cells, whereas it was extremely correlated with illness burden and CAR-T cell viability.”
Full Responses to CAR-T Cell Remedy in Pediatric B-ALL
Following remedy, full remission (CR) to remedy was achieved throughout all sufferers within the remoted extramedullary relapse cohort. Within the refractory, remoted, mixed hematologic relapse cohort, all however one affected person with remoted bone marrow relapse achieved a CR. This affected person died earlier than their analysis.
A complete of 13 and 228 sufferers within the remoted bone marrow and bone marrow plus testes relapse subgroups, respectively, underwent subsequent transplantation in response to protocol standards. Notably, 25 extra sufferers within the remoted bone marrow subgroup underwent transplantation in response to parental request.
Primarily based on these outcomes, a part 1 examine of the routine is underway. Investigators on the examine plan to enroll 12 to 18 sufferers within the examine.
Extra Concerning the Part 2 Trial
Beforehand reported information from this part 2 trial confirmed that co-administration of CD19- and CD22-directed CAR-T cell remedy produced comparatively sturdy EFS charges and a excessive CR charge amongst 225 kids with relapsed or refractory B-ALL or these at a excessive danger of hematologic or extramedullary relapse. CR was achieved in 99% of sufferers (194 sufferers), all of whom achieved minimal residual illness negativity.
The 12-month EFS charges have been 69.2%, 95% and 68.6percentfor sufferers handled for hematologic relapse with out consolidative allogeneic hematopoietic cell transplantation (allo-HSCT; 116 sufferers), remoted testicular relapse (two sufferers) and remoted central nervous system (CNS) relapse (10 sufferers), respectively.
Accordingly, investigators developed a bicistronic CD19/CD20-directed CAR-T cell remedy to boost EFS, OS and security outcomes for sufferers with relapsed or refractory B-ALL, no matter prior publicity to consolidative allo-HSCT after CAR-T cell remedy
Reference
“Security and efficacy of bicistronic CD19/CD22 CAR T cell remedy in childhood B cell acute lymphoblastic leukemia” by Dr. X. Wan, et al. Introduced on the 2024 ASH Annual Assembly.
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