Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma

Abstract

SUMMARY A patient with refractory multiple myeloma received an infusion of CTL019 cells, a cellular therapy consisting of autologous T cells transduced with an anti-CD19 chimeric antigen receptor, after myeloablative chemotherapy (melphalan, 140 mg per square meter of body-surface area) and autologous stem-cell transplantation. Four years earlier, autologous transplantation with a higher melphalan dose (200 mg per square meter) had induced only a partial, transient response. Autologous transplantation followed by treatment with CTL019 cells led to a complete response with no evidence of progression and no measurable serum or urine monoclonal protein at the most recent evaluation, 12 months after treatment. This response was achieved despite the absence of CD19 expression in 99.95% of the patient’s neoplastic plasma cells. (Funded by Novartis and others; ClinicalTrials.gov number, NCT02135406.)

Recent advances in T‐cell immunotherapy for haematological malignancies

“…The Penn group also tested CTL019 in myeloma after autologous transplant and reported one patient who obtained a CR that persisted for 12 months. (Garfall et al 2015) Of note, this response was obtained despite CD19 not being expressed on the majority (99.95%) of the patient’s neoplastic plasma cells.…”

Immunotherapy: An Evolving Paradigm in the Treatment of Advanced Cervical Cancer

“…[67][68][69][70] The most recent strategies have involved the engineering of autologous T-cells with chimeric antigen receptors (CAR) ( Figure 5). 71,72 These CARs are composed of an antigen-binding moiety, derived from the variable region of a monoclonal antibody, linked via a transmembrane motif to a lymphocyte-signaling moiety located in the cytoplasm. Variable, extracellular bindings motifs allow for recognition of tumor-associated antigens, including cell surface specific molecules.…”

“…Unlike traditional cytotoxic therapies, it takes time to establish an antitumor immune response, and target lesions may increase in size or appear to progress early in treatment. 87 With ipilimumab, as an example, 4 distinct patterns of response have been observed: (1) regression of baseline lesion with no new lesions; (2) stable disease followed by a slow, steady decline in tumor burden; (3) delayed response after initial increase in tumor burden; and (4) response after the appearance of new lesions (72). The last 3 patterns of response are not seen with traditional cytotoxic therapies and may be associated with improved immuno-oncologic outcomes.…”

CART‐cells merge into the fast lane of cancer care

“…Genetically modified autologous T cells expressing an Anti-CD19 CAR have shown great promise in a number of different clinical trials [1][2][3][4][5][6]. Unprecedented remission rates of 67%-90% have been observed in adult and pediatric patients with relapsed and refractory acute lymphoblastic lymphoma (ALL).…”

“…Cytokine release syndrome (CRS), an inflammatory process correlating with the in vivo activation and expansion of CD19-CAR T-cells, is the most significant treatment related toxicity. Neurologic toxicity with encephalopathy and seizures is another important side effect [1][2][3][4][5][6]. On target, off tumor effects of CD19-CAR Tcells are fortunately limited to B-cells and B-cell aplasia occurs in patients with CAR T-cell persistence [4,6].…”