Researchers have reported promising results in a Phase I/II trial involving 37 patients with relapsed or refractory B-cell malignancies who were treated with a cord blood-derived natural killer (NK) chimeric antigen receptor (CAR), a cell therapy targeting CD19. Results showed an overall response (OR) rate of 48.6% 100 days after treatment, with one-year progression-free survival (PFS) and overall survival (OS) rates of 32% and 68%, respectively. The trial reported an excellent safety profile, with no cases of cytokine release syndrome (CRS), neurotoxicity or graft-versus-host disease. Another key finding of the trial was the importance of allogeneic cord blood donor selection criteria in the manufacture of CAR NK cells. Cord blood units cryopreserved within 24 hours of collection and those with a low content of nucleated red blood cells were associated with significantly better results. CAR NK cells generated from these units resulted in a one-year PFS rate of 69% and an OS rate of 94%, compared with 5% and 48%, respectively, for units with higher nucleated red cell content or longer collection to cryopreservation times.
Here scientists show that directing a CD19-specific CAR to the T-cell receptor α constant (TRAC) locus not only results in uniform CAR expression in human peripheral blood T cells, but also enhances T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in a mouse model of acute lymphoblastic leukaemia.
A study published this month in the New England Journal of Medicine (NEJM) may change the standard of care for adults who relapse from large B-cell lymphoma.
BigField GEG Tech's insight:
The CAR T cell-based therapy Yescarta (axicabtagene ciloleucel) and manufactured by Kite Pharmaceuticals, was first approved by the U.S. Food and Drug Administration in 2017 as a third-line treatment for adults with large B-cell lymphoma (LBCL), i.e., for those who had already undergone two cycles of failed treatment. The ZUMA-7 clinical trial was therefore set up to determine whether a single infusion of Yescarta is superior to the existing and long-standing standard of second-line care, which is a stem cell transplant after high-dose chemotherapy to kill the lymphoma. According to the results of a clinical trial published December 11th and presented the same day at the American Society of Hematology annual meeting, this treatment is significantly more effective than the current standard of care in treating people with large B-cell lymphoma who relapse after first-line treatment. About 40% of people with LBCL need such second-line treatment, either because their cancer recurs or does not respond adequately to first-line treatment.
In the report Kochenderfer et al discuss the efficacy of autologous T cells expressing a CD19-specific chimeric antigen receptor (CAR) in patients with relapsed diffuse large B-cell lymphoma.
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Researchers have reported promising results in a Phase I/II trial involving 37 patients with relapsed or refractory B-cell malignancies who were treated with a cord blood-derived natural killer (NK) chimeric antigen receptor (CAR), a cell therapy targeting CD19. Results showed an overall response (OR) rate of 48.6% 100 days after treatment, with one-year progression-free survival (PFS) and overall survival (OS) rates of 32% and 68%, respectively. The trial reported an excellent safety profile, with no cases of cytokine release syndrome (CRS), neurotoxicity or graft-versus-host disease. Another key finding of the trial was the importance of allogeneic cord blood donor selection criteria in the manufacture of CAR NK cells. Cord blood units cryopreserved within 24 hours of collection and those with a low content of nucleated red blood cells were associated with significantly better results. CAR NK cells generated from these units resulted in a one-year PFS rate of 69% and an OS rate of 94%, compared with 5% and 48%, respectively, for units with higher nucleated red cell content or longer collection to cryopreservation times.