Chimeric Antigen Receptor T Cell Therapies For Multiple Myeloma

Potential and currently studied settings for the use of car chimeric antigen receptor t cell therapy in the management of multiple myeloma through the natural history of the disease.

Chimeric antigen receptor t cell therapies for multiple myeloma.

Despite promising objective response rates most patients relapse and low levels of bcma on a subset of tumor cells has been suggested as a probable escape mechanism. Chimeric antigen receptors cars are fusion. 5 6 18 20 cars are. 5 6 18 t cells expressing a car can specifically recognize a targeted antigen which is an advantage of car t cells over nonspecific cellular therapies such as allogeneic hematopoietic stem cell transplantation.

There is an unmet need to develop novel therapies for refractory relapsed mm. Cars are artificial fusion proteins that incorporate an antigen recognition domain and t cell signaling domains. In the past few years chimeric antigen receptor car modified t cell therapy for mm. A consensus statement from the european myeloma network philippe moreau 1 pieter sonneveld 2 mario boccadoro 3 gordon cook 4 ma victoria mateos 5 hareth nahi 6 hartmut goldschmidt 7 meletios a.

Dimopoulos 8 paulo lucio 9 joan bladé 10 michel delforge 11 roman. Chimeric antigen receptor t cell therapy for multiple myeloma. Multiple myeloma mm is the second most common hematologic malignancy and remains incurable despite the advent of numerous new drugs such as proteasome inhibitors pis immunomodulatory agents imids and monoclonal antibodies. Disease settings where clinical evaluation of car t cell therapy has been reported advanced relapse refractory disease.

Preclinical studies suggest that bb2121 a chimeric antigen receptor car t cell therapy that targets b cell maturation antigen bcma has potential for the treatment of multiple myeloma. B cell maturation antigen bcma is a validated target for chimeric antigen receptor car t cell therapy in multiple myeloma mm. Multiple myeloma mm is a nearly always incurable malignancy of plasma cells so new approaches to treatment are needed. In this phase 1 study involving patients with relapsed or refractory multiple myeloma we administered bb2121 as a single infusion at doses of 50 10 6 150 10 6 450 10 6 or 800 10.

T cells expressing the car used in this work. B cell maturation antigen bcma is expressed in most cases of mm.