CD19-CART (Shanghai Children's Medical Center)

Infections are increasingly recognized as a complication of chimeric antigen receptor T-cell (CAR-T) therapy however the incidence of infections after non-CD19 targeted CAR-T is not yet known. We report, for the first time, infectious complications after CD30 CAR T-cell treatment for patients with Hodgkin lymphoma and peripheral T-cell lymphoma.We retrospectively evaluated all 64 adult patients with relapsed/refractory CD30+ lymphomas who received anti-CD30 CAR T-cells at a single institution between 2016–2021. We assessed microbiologically confirmed infections within 1 year after cell infusion, censoring for relapse. We calculated infection density (total infections per 100 patient-days-at-risk), and cumulative incidence of infection divided into time periods postinfusion (days 0–28, 29–90, and 91–365). We compared infectious outcomes to a concurrent cohort of CD19 CAR-T recipients (n = 50) at the same institution.Infection density in the first year after CD30 CAR T-cell infusion was 0.131 per 100 patient-days-at-risk, with 17 patients developing 19 total infections including 15 mild, 3 moderate, and 1 severe infection (1-year cumulative incidence of 32%; 95% confidence interval [CI], 19–47]). Infections were primarily viral (30%; 95% CI, 17–44) and most common early after infusion. Far fewer infections were bacterial in CD30 CAR-T recipients (4.9%; 95% CI, 1.3–13), in contrast to the CD19 cohort in which bacterial infections predominated and were more severe.Microbiologically confirmed infections, primarily with respiratory viruses, were most common in the first 28 days after CD30 CAR-T infusion and most were mild. Our findings may have implications for antimicrobial prophylaxis guidelines after CD30 CAR-T therapy.

Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets.

In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45+ BM cells were enriched with human CD45 microbeads. The CD45+ cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis.

In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment.

This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.