A new BCMA-directed CAR T by Arcellx showed impressive 100% overall response rates, with lower cases of side effects normally seen with CAR T, from the Phase I data presented at the recent ASCO meeting.
The CART-ddBMCA product uses a new synthetic binding domain to target the BCMA instead of using an animal or human-derived binder. This allows the product to avoid stoking an immune response that might reduce the effectiveness when given to a patient.
Manufacturing issues causing delays for many patients on CAR T waiting lists have spurred greater need for additional, effective CAR T therapies.
Matthew Figault, MD and colleagues shared data from the Phase I study of 31 patients with relapsed or refractory myeloma. The patients were either triple-refractory or received at least three previous treatment regimens including a proteasome inhibitor (like Velcade or Kyprolis), immunomodulator (like Revlimid) and a CD-38 monocloncal antibody (daratumumab or isatuximab).
Twelve patients (39%) had extramedullary disease where the myeloma has grow outside of the bone marrow to other parts of the body, a condition considered more high risk.
Patients received the typical pre-chemotherapy used in CAR followed by a single infusion of CART-ddBCMA at one of two dose levels. Because of the response rate and lack of high-grade cytokine release syndrome, the final dose selected moving forward is 100 × 10.6
Outcomes at a 12 month review were as follows:
|Very good partial responses||23%|
|Complete response at 1 month||71%|
|Complete response at 6 months||79%|
|Complete response at 12 months||81%|
|Grade 1 or 2 CRS||88%|
|Patients with neurotoxicity at Grade 3 (ICANS)||2|
A phase II study is now planned with expected enrollment at the end of 2022.
Each CAR T product uses different engineering methods. The ARC-SparX platform is combines a universal ART-T cell with an off-the-shelf SparX protein to separate the tumor-finding and tumor-killing functions. The ARC-T cells are only activated to kill the myeloma cells when they find a SparX protein bound to the target cells. The treatment can also be dose-controlled.
Because these study results only include one year of follow-up, it is unclear how long the responses will last compared to other FDA-approved CAR T therapies such as Abecma and Carvykti. The treatment is "clearly working well" according to Dr. Figault and we look forward to seeing additional data.
about the author
Myeloma survivor, patient advocate, wife, mom of 6. Believer that patients can help accelerate a cure by weighing in and participating in clinical research. Founder of Myeloma Crowd by HealthTree and the HealthTree Foundation.