CAR-T cell treatment for multiple myeloma – the landscape so far
Chimeric Antigen Receptor (CAR) T cell therapy has been approved in Australia for forms of leukaemia and lymphoma for a while now, but we are still awaiting adequate evidence that CAR-T cell therapy works effectively in myeloma.
CAR-T cell therapy genetically modifies T-cells to hunt out and find a protein (CD19) that is found on lymphoma and leukaemia cells. Unfortunately, myeloma cells don’t frequently express the CD19 protein. So, in order to use CAR-T cell technology to treat myeloma, researchers need to first identify a suitable protein that can be targeted. The good news is this field is rapidly evolving. There are more than 50 ongoing clinical trials worldwide assessing different CAR-T cell designs (autologous or allogenic) or targets1.
B-cell maturation antigen (BCMA) is a cell surface protein that is universally expressed on malignant myeloma cells and is being used by a number of organisations as the target for myeloma CAR-T cell therapy. A trial called CARTITUDE-1 using Janssens autologous anti- BMCA CAR-T cell therapy product is well underway in patients with relapsed or refractory myeloma. Top line results were recently presented after 11.5 months of follow up. All 29 treated patients showed deep and durable responses. 86% of patients achieved complete responses2.
Anti- BMCA CAR-T cell therapy shows the best evidence of efficacy and safety so far. Analysis of 20 single target anti-BCMA studies show an overall response rate of 84% and a complete response of 43%1. Most common side effects included cytokine release syndrome, neurotoxicity and haematological toxicities such as neutropenia, leukopenia, anaemia and thrombopenia. There are at least another five cell targets being investigated for multiple myeloma CAR-T cell therapy, however it is too early to assess their efficacy and safety.
Autologous CAR-T cell therapy is appealing as there is less risk of graft vs host disease, however many patients do not have the ability to replicate enough CAR-T cells to harvest for treatment. Furthermore, the time taken to grow and harvest the T-cells is often precious time patients with multiple myeloma do not have by the time CAR-T cell therapy is offered. As a result, trials are now underway with allogenic CAR-T cell therapy. Issues that need to be overcome include graft vs host disease and a lack of persistence if the host immune system eliminates the genetically modified T cells. However, it is believed that this will be the path of future treatment. The consistency in treatment, speed to end product and ability to mass produce the cells making substantial cost savings make it very appealing.
The majority of multiple myeloma CAR-T cell trials are being conducted in the US however there are currently trials in Australia. Please speak with your treating haematologist to learn more.
- Gagelmann N, Riecken K, Wolschke C et al Nature, June 2020 https://doi.org/10.1038/s41375-020-0930-x