Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells are associated with clinical outcomes in NHL.

After treatment with chimeric antigen receptor (CAR) T cells, interleukin-15 (IL-15) elevation and CAR T-cell expansion are associated with non-Hodgkin lymphoma (NHL) outcomes. However, the association of preinfusion CAR product T-cell functionality with clinical outcomes has not been reported. A single-cell analysis of the preinfusion CD19 CAR product from patients with NHL demonstrated that CAR products contain polyfunctional T-cell subsets capable of deploying multiple immune programs represented by cytokines and chemokines, including interferon-γ, IL-17A, IL-8, and macrophage inflammatory protein 1α. A prespecified T-cell polyfunctionality strength index (PSI) applied to preinfusion CAR product was significantly associated with clinical response, and PSI combined with CAR T-cell expansion or pretreatment serum IL-15 levels conferred additional significance. Within the total product cell population, associations with clinical outcomes were greater with polyfunctional CD4+ T cells compared with CD8+ cells. Grade ≥3 cytokine release syndrome was associated with polyfunctional T cells, and both grade ≥3 neurologic toxicity and antitumor efficacy were associated with polyfunctional IL-17A-producing T cells. The findings in this exploratory study show that a preinfusion CAR product T-cell subset with a definable polyfunctional profile has a major association with clinical outcomes of CAR T-cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT00924326.

Kaposi Sarcoma Inflammatory Cytokine Syndrome Presenting as Infection: A Case Report.

Kaposi sarcoma inflammatory cytokine syndrome is a rare and fatal malignancy that is challenging to treat. The syndrome appears in individuals who are both human immunodeficiency virus and human herpesvirus 8 positive. The diagnosis of disease is challenging because its presentation mimics sepsis and it has a high mortality rate. A bone marrow biopsy is necessary for definitive diagnosis. This case report discusses a 40-year-old human immunodeficiency virus infection-positive African American male who presented to the emergency department with a chief complaint of left hallux pain in January 2018 after a trip to a nail salon in December 2017. Radiographic and magnetic resonance images suggested osteomyelitis of the distal phalanx, and Gram stain of bone showed gram-negative rods. The patient was started on antibiotic therapy for presumed osteomyelitis. As the patient's status deteriorated, a partial hallux amputation was then performed. Intraoperative specimens were negative for bacterial involvement, but pathology was positive for Kaposi sarcoma. During a 7-month progression, the patient's hematologic and overall status continued to decline. Despite diagnostic and treatment guidelines being followed, the patient died from this illness in July 2018. This case is interesting because of the atypical presentation of Kaposi sarcoma and highlights the rapid progression of the disease.