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CAR-T cell therapy a story of opportunities and challenges in MM

CAR-T cell therapy a story of opportunities and challenges in MM

Chimeric antigen receptor (CAR) T cell therapies can help patients with otherwise refractory cases of multiple myeloma, but patients have to overcome significant hurdles to access the therapy.

Chimeric antigen receptor (CAR) T cell therapies have significant potential to change the treatment landscape for patients with multiple myeloma (MM), but a new review article notes that the therapeutic strategy is significantly limited by challenges – both logistical and clinical.

Sign up Blood and Lymph Cancer: Goals and Therapycorresponding author Christin B. DeStefano, MD, of Walter Reed National Military Medical Center, and colleagues, said new therapies have led to improvements in outcomes for people with MM, and CAR T-cell therapies may further improve survival rates, especially for humans. with refractory disease.

“[Y]et their logistical and clinical limitations must be acknowledged to further improve patient outcomes,” cautioned DeStefano and colleagues.

The technology that evolved into CAR T cell therapies has been around for over 3 decades, but the first CAR T cell therapy for MM was only approved by the FDA last year. The therapy involves taking a patient’s T cells and genetically modifying them before infusing them back into the patient.

“After infusion, CAR T cells bind to their target antigen(s), proliferate, release tumor antigens, induce epitope spreading and recruit other immune cells, ultimately leading to a multifaceted immune response that results in robust cell killing,” DeStefano and colleagues said.

There are now 2 FDA-approved CAR T cell therapies for MM, idecaptagene vicleucel (ide cell; Abecma) and ciltacabtagene autoleucel (cilta cell; Carvykti). Both are approved for relapsed or refractory MM after a minimum of 4 lines of therapy.

The authors said it is difficult to compare the efficacy of the 2 approved therapies, due to a lack of direct comparison clinical trials. However, the researchers said there is real evidence to suggest that both therapies outperform conventional therapies.

But given the logistics and manufacturing of the treatments, their success will depend on more than just efficacy. The therapy can take up to 4 weeks to make as each therapy is made to order for each individual patient.

Timely treatment requires consideration of production slot availability, salvage treatment timing, pre-CAR T-cell work, and testing and apheresis in the treatment facility,” said DeStefano and colleagues.

In addition, there is a significant risk of product failure, as myeloma involves changes in T cells that can make them unsuitable for the manufacturing process. Supply chain issues can also create problems by limiting access to medicines needed for treatment.

“When approaching CAR T cell therapies under such constraints, physicians may delay the use of CAR T cell therapy until necessary conditioning and supportive drugs are available,” they said.

Other logistical issues include a lack of available centers that can provide the therapy, and a price tag of more than $400,000 for both therapies, DeStefano and colleagues wrote.

Even if the therapy is successfully manufactured and administered, the authors noted that many patients will also face clinical challenges, including toxicities such as cytokine release syndrome and infections.

In addition, some patients will develop resistance and the mechanisms behind resistance are not yet clear. The researchers said other questions worthy of additional study include how best to treat patients who progress after CAR-T therapy and how best to sequence therapies.

“Ongoing studies are assessing the efficacy of CAR T cells in previous lines of therapy, as well as new targets and methods to reduce production time,” they concluded.

Reference

Rendo MJ, Joseph JJ, Phan LM, DeStefano CB. CAR T-cell therapy for patients with multiple myeloma: current evidence and challenges. Blood Lymphatic Cancer. 2022;12:119-136. doi:10.2147/BLCTT.S327016