ASH 2022: New CAR T Binding Method Explored in Multiple Myeloma

B-Cell Maturation Agent (BCMA) is the most common and seemingly effective target for CAR T therapy today. But because current products are not as durable as patients need, new targets and technologies are being explored.  

In a poster session at the recent Amercian Society of Hematology meeting, Matthew Figault, MD, MS shared a Phase I clinical trial testing a new binding method for a BCMA-targeted CAR T therapy for patients with relapsed or refractory multiple myeloma. 

CART-ddBCMA is an autologous anti-BCMA CAR T cell therapy with a new synthetic binding site to the myeloma cancer cell. It is made of 73 amino acids or proteins called D-Domain which may be an improvement over the current type of binding site called scFV. 

The theory is that an improvement in the binding site of the CAR T to the cancer cell may make it more effective and hopefully last longer. If you want to learn more about the current FDA-approved CAR T therapies, please visit this Healthtree video.

At the last data-cut off, 38 patients received CART-ddBCMA at 2 different doses, 100 and 300x10⁶ CAR T cells. Median follow-up after CART-ddBCMA infusion was 12.1 months.

Side effects included:

• Cytokine Release Syndrome Grade 1&2 in the low dose group at 94% and 83% in the high dose group
• Neurotoxicity was seen in 7 patients at grades 1, 2, and 3 at both doses, but was resolved with standard management
• There was no delayed neurotoxicity or Parkinson-like events
• There were no other off-target effects, which is good news
• There were no manufacturing failures

Response rates:

• There was 100 % overall response rate, which is excellent
• Progression-free survival at 6 months was 92%, at 12 months 73% and at 18 months 65%

The details of the study included only relapsed multiple myeloma patients that have had at least 3 prior standard treatment lines and all the patients are triple refractory.  The median patient had 5 prior lines of therapy.  The median age was 66 years old. These patients had lymphodepletion chemotherapy to prepare them before getting the CAR T infusion.

Thirty-two (32) patients got the lower dose and 6 got the higher dose of CAR T cells. The median duration of response has not yet been reached. 

We will watch for updates on this new CAR T product to see if the new type of binding site improves outcomes. Myeloma researchers are looking for any and all ways to improve the durability of this important treatment.