Fig. 1

Overview of BCMA CAR-T-cell therapies used to date in multiple myeloma (MM) patients. Twenty-three different BCMA CAR-T-cell products involving 640 patients were identified. All products were derived from autologous T cells collected by apheresis (1), and enriched and activated ex vivo by anti-CD3/CD28 stimulation ± interleukin (IL)-2 or by single anti-CD3 stimulation ± IL-2 (2). The CAR gene was introduced in the T cells by lentiviral or retroviral transduction, or using a transposon (3). The resultant CAR-T cells were then further expanded (4) and administered to the patient by intravenous infusion, usually after lymphodepleting conditioning with cyclophosphamide (CP) ± fludarabine (Flu) (5). The BCMA CAR-T-cell products used to date can be divided into three groups based on the origin of the extracellular antigen-recognition domain: murine, human(ized), or alpaca/llama. The murine and human(ized) CAR constructs are usually based on the antigen-binding domain of a monoclonal antibody (mAb) in single-chain fragment variable (scFv) format with the variable regions of the heavy (V_H) and light chains (V_L) linked together in a single chain. Alpaca/llama BCMA CAR constructs are based on the structure of a camelid nanobody containing one or more V_HH domains. In addition, the intracellular co-stimulatory domain allows a further subdivision in 4-1BB-based and CD28-based BCMA CAR-T-cell products. Age = studies in whom the median patient age was ≥ or < 60 years. CO+ = co-stimulatory domain. HR = studies with a median of ≥ or < 50% high-risk myeloma patients (based on cytogenetics and/or International Staging System [ISS] score). n = number of patients. PLT = studies in which the median number of prior lines of therapy was ≥ or < 5. TM = transmembrane domain.