Despite being administered such different infusion doses, at 8 years plus follow-up, both patients remain in deep molecular remission with CAR-T cells still present. B cells remain wiped out. “The B-cell aplasia is expected,” Tanya Siddiqi, MD, hematologist/oncologist at City of Hope, Duarte, California, told Cancer Therapy Advisor.
B-cell aplasia is typical among patients who respond to CD19-directed CAR-T therapy given that B cells also express the target antigen, CD19. “To know that [CAR-T cells] can survive and be measurable 8 years out is interesting,” she said.
“That’s a goal that a lot of other CAR-T cell studies are trying to get to — to see how can their CAR-T cells persist, essentially forever in patients, so that they can control the disease forever,” said Dr Siddiqi, who was not involved in the current study.
In addition to detecting CAR-T cells at long-term follow-up, researchers monitored the CAR-T cells over time, noticing several trends. First, early on, CD8+ CAR-T cells expanded rapidly followed by eventual expansion of CD4+ CAR-T cells. CD4+ CAR-T cells appear to eventually dominate the overall pool of CAR-T cells, with CD8+ CAR-T cells making up only a small portion. In contrast, the normal CD4+ and CD8+ T cells that were not genetically engineered to express a CAR targeted to CD19 maintained a relatively stable composition of CD4+ and CD8+ T cells over time.
“It has become clear that the quality of the infused T-cell product plays a key role in outcome,” Kathleen Dorritie, MD, Hematologist/Medical Oncologist, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, told Cancer Therapy Advisor. She was not involved in the current study. “This study suggests that both the CD8+ and CD4+ T cells play important, but different, roles in the antitumor response.”
Another observed trend was that CAR-T cells expressed both inhibition and activation regulatory markers over the years. During an interview with Cancer Therapy Advisor, study presenter Jan Joseph Melenhorst, PhD, University of Pennsylvania, conjectured that because of this balance between positive and negative signals, these patients still have these CAR-T cells. He explained that there’s a level of constant activation, but the activation is controlled, “so that cells do not run out of steam.”