First U.S. CAR-T Trial for AL Amyloidosis Shows Promise | Heather Landau, MD

Hi, my name is Heather Landau and I'm from Memorial Sloan Kettering Cancer Center and I'm delighted to share the results of Nexacart 2, the first US trial of a BCMA-directed CAR T cell for patients with AL amyloidosis. Patients with AL amyloidosis, there are about 30,000 patients with relapsed or refractory AL amyloidosis who are living with or will develop this in the US that have no FDA-approved drugs available and that prompted us to study this novel BCMA-directed CAR T cell for this patient population because again, they have a very high unmet medical need. What we found in the first 20 patients is that the patients achieve a very deep and rapid hematologic response with 75% of patients achieving a complete hematologic response in a median of seven days. Patients who have an immunofixation or a monoclonal M-spike often take a little bit longer to achieve a complete hematologic response, but those patients, at least four of the remaining patients are expected to evolve into a complete hematologic response because they are already MRD negative or minimal residual disease negative in the bone marrow. We also see this prompt reduction in free light chains and M-spikes translate into organ improvement in 75% of patients with cardiac involvement and three out of five patients with renal involvement and in our single patient with liver involvement. So seven out of ten patients have achieved an organ response at this early stage in our clinical trial, which was started in June of 2024 and is accruing rapidly given the unmet medical need of these patient population. The most important thing is that the safety of this particular CAR T cell is really quite remarkable, although 80% of patients or 75% of patients experience cytokine release syndrome, which is common with CAR T cells. All patients develop low-grade, meaning grade 1 to 2, and it's really very manageable with tocilizumab, so it happens very promptly within one to three days and resolves in a median of one day. This product has not been associated with any neurotoxicity of any kind, so it's really been very, very safe for patients. So amongst all 20 patients treated, the bottom line is that 75% of patients are in a complete hematologic response. 16 out of 18 valuable patients are MRD negative in the bone marrow. Every patient experienced a rapid and deep hematologic response. We only have had one progressor that was the only patient who did not normalize their periprotein after treatment and subsequently progressed. One patient with advanced kidney disease did die six months post after the treatment was delivered, but deemed unrelated to the CAR T cell itself because that patient was dialysis dependent and acquired a catheter-related infection, which resulted in her unfortunate death. But we're very excited. All other patients are continuing in hematologic response and no other organ or hematologic progressor, so 18 out of 20 patients remain in response and continue to do well. This treatment has also led our patients to not only respond by hematologic parameters, but also symptomatically, and patients are really clinically well after this therapy. So the phase two trial is open and accruing across the country, and we're excited to complete the trial in the next few months. If our videos have helped you in any way and you're able to, please consider making a donation to help us continue this important work. Your gift will go three times as far when we reach $500,000 by the end of the year. Every contribution, big or small, makes a difference, and we're deeply grateful for your support.