New treatment strategies for multiple myeloma

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Published: 10 Dec 2017
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Dr James Kochenderfer - National Cancer Institute, Bethesda, USA

Dr Kochenderfer speaks with ecancer at the ASH 2017 annual meeting about clinical activity seen with anti-BCMA CAR T-cell therapy in a phase 1 study of people with heavily pre-treated multiple myeloma. 

Read the news story or watch the press conference for more information. 

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

This work evolves from other CAR work. CAR T-cells, or chimeric antigen receptor T-cells, have been a very promising therapy now for about ten years for various haematological malignancies. In an effort to develop a therapy for multiple myeloma I decided to target B-cell maturation antigen which is abbreviated BCMA and is expressed mainly on plasma cells. It’s a target that is very promising because its expression is limited mainly to plasma cells so it doesn’t damage other areas of the body when we infuse these anti-BCMA CAR T-cells.

What was the method?

The work that I’m presenting at this press conference was about a multi-centre clinical trial where we tested a cell product called BB2121. This product is a T-cell product that is an autologous T-cell that expresses a CAR with a form of BB moiety, a T-cell activation moiety, and part of a monoclonal antibody that targets the BCMA.

What did you find?

We found in the 21 patients we treated in a dose escalation phase I study that the first dose level where we gave 50 million CAR T-cells that the dose was ineffective and all three patients rapidly had progression of their multiple myeloma. In the eighteen patients after the first dose level where we gave between 150 and 800 million CAR T-cells 94% of patients had an objective response by standard multiple myeloma staging criteria, so 17 out of 18 had a response. We’ve found that these responses have been durable, five patients had responses that lasted at least a year. Many patients still have ongoing responses and the responses tend to be deepening over time with patients converting from partial remissions to complete remissions over time.

What conclusions can be drawn from this?

The conclusions are that this is a very effective and promising therapy for multiple myeloma. It’s very different from any other multiple myeloma therapy. It’s a living T-cell product that can persist in the patient and last for months and continue to control myeloma and fight myeloma for an extended period of time. We’ve seen very impressive responses in a very heavily pre-treated patient population; patients who have had every known therapy for multiple myeloma can still have very great responses to this therapy with durable remissions lasting in our longest case so far up to 68 weeks with many ongoing responses.

Any adverse effects we should know about?

We have had adverse effects. Like all CAR T-cell products we’ve seen cytokine release syndrome. We’ve seen that in 71% of patients but it has been very mild and none of the patients have had grade 3 or greater cytokine release syndrome. Neurologic toxicity has also been mild in general with a very favourable toxicity profile in my experience compared to other T-cell products.