科研之友
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摘要
The malignant plasma cell clone in patients with multiple myeloma (MM) is represented by the production of paraprotein, usually a single abnormal unique monoclonal heavy and/or light chain with constant isotype.1 Switching of the paraprotein or transient presence of oligoclonal bands on serum immunofixation electrophoresis occurs in up to 73% of patients after autologous stem cell transplantation (ASCT) and high-dose chemotherapy.2-4 The emergence of these abnormal protein bands (APBs) may represent more durable immune reconstitution and be associated with favorable prognosis in that setting.4-7 B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy is emerging as a promising treatment for patients with relapsed or refractory (R/R) MM. BCMA CAR T-cell therapy resulted in high overall response rates (range, 64%-88%) in multiple recent clinical trials.8-11 CAR T-cell therapy, like ASCT and high-dose chemotherapy, involves the activation and regulation of the immune system.12 Specifically, plasma cells and mature B lymphocytes targeted by BCMA CAR T cells are also integral components of the humoral immune system. However, the prevalence and clinical significance of APBs in patients with MM after CAR T-cell therapy remain unclear. Between 1 January 2018 and 1 February 2020, 12 consecutive patients with R/R MM were enrolled in a clinical trial of BCMA CAR T cells (registered at www.clinicaltrials.gov as #NCT04500431). This study was approved by the Tongji Hospital of Tongji University Ethics Committee, and written informed consent was provided by each patient. All studies were conducted in accordance with the Declaration of Helsinki. Full details on BCMA CAR T-cell manufacturing and clinical procedures are provided in the data supplement. In the 12 patients treated, the overall response rate was 75% (9 of 12), with a strict complete response (sCR) in 67% (8 of 12) and a very good partial response in 8% (1 of 12; Figure 1A). Quantitative real-time polymerase chain reaction showed those patients with response (partial response or better) had a peak in CAR transgene copies in peripheral blood between days 7 and 21, which then dropped to low or undetectable levels by 6 months (supplemental Figure 1). With a median follow-up of 15 months (range, 4-26), the median PFS and the median overall survival were 12 months and not reached, respectively (Figure 1B-C). The adverse events within 30 days after infusion were well tolerated. Toxic hematologic effects were the most common grade $3 events, including neutropenia (67%), anemia (42%), and thrombocytopenia (33%). A total of 11 patients (92%) had cytokine release syndrome, which was grade 1 or 2 in 9 patients (75%) and grade 3 in 2 patients (17%). Only 1 patient experienced grade 1 neurologic toxicity. Three patients (25%) received tocilizumab and/or glucocorticoids. No patients experienced severe infection within 30 days after infusion. Detailed patient baseline characteristics, treatment response, and toxicities are described in supplemental Tables 1 and 2. During follow-up after CAR T-cell therapy, we observed that 4 patients (33%) had APBs on serum immunofixation electrophoresis distinct from the paraprotein present at diagnosis, which were below the level
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单位同济大学; 浙江大学
