ICML 2025 | MB-CART19.1 cell therapy for R/R CD19+ hematological malignancies with CNS involvement

Relapsed/refractory hematological malignancies involving the central nervous system are some of the toughest cases we face. Outcomes are poor and treatment options are usually very limited, and the good news is that CAR T-cell can work for those patients. We definitely know that, but here’s the catch: many high-risk patients never get to CAR T-cell infusion, and that’s mainly because of delayed logistical issues or rapid CNS progression. So the disease moves faster than all of the logistical processes, but here we have good news that academic place of care-produced CD19 CAR T-cells may shorten the time to treatment for those rapidly progressing patients. So really, we have our real-world data in patients with relapsed/refractory CD19-positive hematological malignancies with central nervous system involvement that was treated with the autologous CD19-directed CAR T-cells that was produced using an 8 to 12-day protocol in our GMP-compliant place of care facility under hospital exemption rule. And since 2022 until 2024, we already treated nine of those relapsed/refractory patients with CNS involvement. And these patients were really high-risk; previously, most of them had previously had three or more lines of therapy, and all of them were refractory to their last line of therapy, and for all of those patients, CAR T-cells were produced successfully, and the most probably the most important thing is that the turnaround time was very short, so only seven days from first thoughts about CAR T-cells to apheresis and only 13 days from apheresis to CAR T-cell infusion, and also notably, almost 80 percent of patients received their CAR T-cell fresh, so no freezing and no delays because of that, and I think those are very important things that led to high response rates for our patients. So I just want to highlight that our produce place of care MBCD19 CAR T-cell therapy resulted in 89% of patients with CNS involvement achieving complete response both systemically and in the central nervous system. Unfortunately, the story doesn’t end here; despite achieving complete response, four of those patients relapsed, two in the CNS, one systemically, and one had both CNS and systemic progression. Toxicity also is important, and cytokine release syndrome was observed in 67% of patients, but mostly low-grade; only one grade 3 series was observed, and also only two patients experienced ICANS, one of them severe, and that was the patient with acute lymphoblastic leukemia with high tumor burden that is known to be higher risk for neurotoxicity. So to sum it up, really, our place of care-produced CD19-directed fresh CAR T-cell therapy is characterized by a short turnaround time and results in high clinical CNS response rates. Unfortunately, relapses are quite often, and this highlights the importance of new treatment strategies, including consolidation, maintenance therapy, or combined modalities to have better outcomes for those patients. This is very important because in previous clinical studies, many of those patients with central nervous system involvement were excluded because we didn’t know if CAR T-cells can penetrate the blood-brain barrier, but the good news is that in our study, we for all tested patients, we detected CAR T cells in cerebrospinal fluid that definitely showed that CAR T-cells really can penetrate the blood-brain barrier, and also that leads to great response to the central nervous system. And most importantly, those CAR T-cells were persisting, and at six months, for most of the patients, more than 80% had still detectable CAR T-cells in their cerebrospinal fluid.

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