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 multiple myeloma cases, but patients must overcome significant barriers to access 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.
write in Blood and lymphatic cancer: targets and treatmentcorresponding author Christin B. DeStefano, MD, of Walter Reed National Military Medical Center, and colleagues said that new therapies have led to improved outcomes for people with MM, and that CAR T- cell can further improve survival rates, especially for people with refractory disease.
“[Y]and their logistical and clinical limitations must be recognized to further improve patient outcomes,” warned DeStefano and colleagues.
The technology that has developed 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 injecting them back into the patient.
“After infusion, CAR T cells bind to their target antigen(s), proliferate, release tumor antigens, induce epitope spread, and recruit other immune cells, ultimately orchestrating a response multi-faceted immune response resulting in robust cell destruction,” DeStefano and colleagues said.
There are now 2 FDA-approved CAR T-cell therapies for MM, idecaptagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti). Both are approved for relapsed or refractory MM after at least 4 lines of treatment.
The authors stated that it was difficult to compare the effectiveness of the 2 approved therapies, due to a lack of direct comparison clinical trials. However, the researchers said there is concrete evidence to suggest that both therapies outperform conventional therapies.
However, given the logistics and manufacturing of the treatments, their success will not only depend on their effectiveness. Therapy manufacturing can take up to 4 weeks as each therapy is made to order for each patient.
“Timely processing should consider the availability of manufacturing slots, the timing of salvage processing, pre-CAR T-cell workup and testing, and apheresis at the processing facility,” they said. said DeStefano and his colleagues.
Additionally, there is a significant risk of product failure, as myeloma is associated with changes in T cells that may render them unsuitable for the manufacturing process. Supply chain issues can also cause problems by limiting access to the drugs needed for treatment.
“When approaching CAR T-cell therapies with such limitations, physicians may withhold the use of CAR T-cell therapy until necessary conditioning and supportive medications are available,” they wrote. declared.
Other logistical issues include a lack of available centers that can provide the therapy and a price tag of more than $400,000 for either therapy, DeStefano and colleagues wrote.
Even if the therapy is successfully manufactured and infused, the authors noted that many patients will also face clinical challenges, including toxicities such as cytokine release syndrome and infections.
Additionally, some patients will develop resistance, and the mechanisms underlying the resistance are not yet clear. The researchers said other questions worthy of further study include how best to treat patients who progress after CAR-T therapy and how best to sequence therapies.
“Ongoing studies are evaluating the efficacy of CAR T cells in the first lines of treatment, as well as new targets and methods to reduce manufacturing time,” they concluded.
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