CD19-targeted chimeric antigen receptor (CAR) T cell therapy is an effective treatment for diffuse large B cell lymphoma (DLBCL). In addition to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), B cell aplasia and hypogammaglobulinemia are common toxicities predisposing these patients to infections. We analyzed 60 patients with DLBCL treated with FDA-approved CD19 CAR T cells and report the incidence, risk factors, and management of infections during the first year after treatment. A total of 101 infectious events were observed, including 25 mild, 51 moderate, 23 severe, 1 life-threatening, and 1 fatal infection. Bacteria were the most common causative pathogens. The cumulative incidence of overall, bacterial, severe bacterial, viral, and fungal infection at 1 year were 63.3%, 57.2%, 29.6%, 44.7%, and 4%, respectively. In multivariate analyses, the use of systemic corticosteroids for the management of CRS or ICANS was associated with an increased risk of infections and prolonged admission. Impaired performance status and history of infections within 30 days before CAR T cell therapy was a risk factor for severe bacterial infection. In conclusion, infections were common within the first 60 days after CAR T cell therapy, however, they were not associated with an increased risk of death.

Abstract Cytokine release syndrome (CRS) immune effector cell–associated neurotoxicity syndrome are the most notable toxicities of CD19 chimeric antigen receptor (CAR) T-cell therapy. In addition, CAR T-cell–mediated toxicities can involve any organ system, with varied impacts on outcomes, depending on patient factors and involved organs. We performed detailed analysis of organ-specific toxicities and their association with outcomes in 60 patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 CAR T cells by assessing all toxicities in organ-based groups during the first year posttreatment. We observed 539 grade ≥2 and 289 grade ≥3 toxicities. Common grade ≥3 toxicities included hematological, metabolic, infectious, and neurological complications, with corresponding 1-year cumulative incidence of 57.7%, 54.8%, 35.4%, and 18.3%, respectively. Patients with impaired performance status had a higher risk of grade ≥3 metabolic complications, whereas elevated lactate dehydrogenase was associated with higher risks of grade ≥3 neurological and pulmonary toxicities. CRS was associated with higher incidence of grade ≥3 metabolic, pulmonary, and neurologic complications. The 1-year nonrelapse mortality and overall survival were 1.7% and 69%, respectively. Only grade ≥3 pulmonary toxicities were associated with an increased mortality risk. In summary, toxicity burdens after CD19 CAR T-cell therapy were high and varied by organ systems. Most toxicities were manageable and were rarely associated with mortality. Our study emphasizes the importance of toxicity assessment, which could serve as a benchmark for further research to reduce symptom burdens and improve tolerability in patients treated with CAR T cells.

Summary The International Prognostic Index (IPI) is the most widely used score for non‐Hodgkin lymphoma but lacks the ability to identify a high‐risk population in diffuse large B‐cell lymphoma (DLBCL). Low absolute lymphocyte count and high monocytes have proved to be unfavourable factors. Red‐cell distribution width (RDW) has been associated with inflammation and beta‐2 microglobulin (B2M) with tumour load. The retrospective study included 992 patients with DLBCL treated with R‐CHOP. In the multivariate analysis, age, Eastern Cooperative Oncology Group performance status (ECOG‐PS), stage, bulky mass, B2M, RDW, and lymphocyte/monocyte ratio (LMR) were independently related to progression‐free survival (PFS). A new prognosis score was generated with these variables including age categorized into three groups (0, 1, 2 points); ECOG ≥ 3–4 with two; stage III/IV, bulky mass, high B2M, LMR < 2·25 and RDW > 0·96 with one each; for a maximum of 9. This score could improve the discrimination of a very high‐risk subgroup with five‐year PFS and overall survival (OS) of 19% and 24% versus 45% and 59% of R (revised)‐IPI respectively. This score also showed greater predictive ability than IPI. A new score is presented including complete blood cell count variables and B2M, which are readily available in real‐life practice without additional tests. Compared to R‐IPI, it shows a more precise high‐risk assessment and risk discrimination for both PFS and OS.

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