CAR T-cell therapy has revolutionized myeloma treatment. The impressive clinical trial results have raised the ceiling for all myeloma treatments as the FDA looks to approve new therapies for myeloma. 

Abecma, Bristol Myers Squibb's CAR T-cell therapy, had an overall response rate was 72% and a complete response rate was 28%.

CARVYKTI has an overall response rate of 98% with a median follow-up of 27.7 months in a heavily pretreated population, with 83% of those patients having achieved at least a stringent complete response (sCR), the deepest level of measurement before MRD (minimal residual disease) in Johnson and Johnson's CARTITUDE-1 study, which led to its approval in 2022. 

The Beauty of Myeloma CAR-T Cell Therapy 

Part of what makes CAR T-cell therapy so revolutionary is its mechanism of action.

T-cells are harvested from a qualifying patient using a process called apheresis (this is sometimes referred to as leukapheresis.) After the T-cells are collected, they are safely stored and sent to a lab in which they are genetically engineered to target multiple myeloma. In the case of both Abecma and CARVYKTI, t-cells are engineered to recognize the BCMA protein, commonly found on the surface of myeloma cells and destroy them. 

The T-cells are then expanded by growing cells in the laboratory until there are millions of them. This can take some time, which we will mention more below. After the sufficient amount is reached, they are frozen and sent back to the academic center from which they came. 

Note that some patient might even receive some type of bridging or consolidation therapy to make room for the new T-cells in between their T-cell collection and their infusion. 

The patients then receive their new and improved T-cells through an infusion, similar to a blood transfusion. This will usually be accompanied by other prophylactic medicines to prevent common issues such as CRS (cytokine release syndrome), ICANS (neurological toxicity), and serious infections. 

Patients are then monitored for complications and given time to recover. 

You can learn more about Abecma and CARVYKTI in our free HealthTree University courses.

Problems with CAR-T Therapy for Myeloma 

While extremely effective, CAR T-cell therapy isn't the perfect solution for myeloma patients. 

1. It's currently approved only as a fourth line of therapy, which means the only people eligible for this ground-breaking treatment are usually past other treatment options and have exhausted immune systems.
2. The cost can be high as patients are working with insurance to make sure that they can afford a treatment (outside of a clinical trial). In some cases, the cost can be upwards of $400,000 USD. 
3. It doesn't work for all patients. Although there have been impressive results from CAR T-cell therapy, it's not a cure for multiple myeloma.
4. As mentioned above, many of the patients who do qualify for CAR-T can't wait the allotted amount of time it takes to collect T-cells, send them to a lab, have them re-engineered, sent back, and then administered again to the patient. They either need bridging therapy to control their disease or need to shift to a new regimen altogether. 

Can CAR T-cell Therapy Be Improved Through a Direct Injection? 

In-vivo CAR T-cell therapy could solve a lot of the problems listed above, namely the financial costs and the time that it takes to produce and re-engineer the T-cells. 

This version of CAR T-cell therapy would test the creation of CAR T-cells within the patient themselves instead of having them produced in a lab. The concept of a similar injection was tested pre-clinically (meaning outside of a clinical trial) within mice. The injection was successful. 

At the 2023 ASH Conference, Umoja Biopharma and Interius BioTherapeutics both presented separate abstracts in which they shared their ground-breaking, preclinical data about their unique projects, using lentiviral injection to deliver CAR genes to the T-cells of an animal. 

In his informative article on this subject, William A. Haseltine shares: 

"Lentiviral vectors are commonly used to deliver genes in cell therapies, and CAR T therapy is no exception. This vector is made from nonreplicating forms of the lentivirus HIV. Researchers take advantage of HIV’s propensity to infect T cells by inserting synthetic genes into the virus. The virus then delivers the gene package to the desired cell."

In both products noted above, the humanized mice with blood cancer successfully formed CAR T cells within seven days of receiving the injection. All of the mice experienced complete tumor eradication and protection from developing future tumors. 

What Could This Mean for the Future of CAR T-Cell Therapy? 

While this data is extremely early in terms of a human-viable product, the implications of this research are exciting. This could lead to a financially accessible, quicker CAR-T product that allows all myeloma patients to easily access a groundbreaking and lifesaving therapy. 

These kinds of advances are vital as we search for a myeloma cure for all myeloma patients, regardless of social class, race, location, or any other disparity that might keep them from normally accessing important therapies such as this. Stay tuned for more information on CAR-T therapies.