Figure 1.

Cytomegalovirus reactivation occurs at moderate incidence afer CD19 CAR T-cell therapy and can be treated by cytomegalovirus-specific therapies. Cytomegalovirus (CMV) reactivation was defined as >400 IU/mL copies of CMV DNA. (A) Distribution of CMV DNA quantitative polymerase chain reaction (qPCR) testing after CD19 chimeric antigen receptor (CAR) T-cell therapy. CMV DNA qPCR testing occurred primarily during the first 180 days after CD19 CAR T-cell therapy. Testing occurred at the time points indicated by a dot. Red dots indicate CMV reactivation and blue dots indicate no CMV reactivation. (B) Cumulative incidence of CMV reactivation in CMV-seropositive patients. The cumulative incidence was 44% (95% confidence interval [CI]: 25-62) by day+100. (C) Clinical course of patients with CMV reactivation. Fourteen of 65 patients reactivated CMV. Four of these patients were not treated with CMV specific therapy (upper facet). Ten of these patients were treated with CMV-specific therapy (lower facet). Three of 4 patients who were not treated with CMV-specific therapy resolved the infection without intervention as defined by a subsequent CMV DNA qPCR test <400 IU/mL (blue dot, upper facet, below dashed line). The CMV status of the fourth untreated patient was indeterminate due to the lack of follow up CMV DNA qPCR testing. Six of the 10 patients treated with anti-CMV therapy responded to treatment as defined by a subsequent CMV DNA qPCR test ≤400 IU/mL (blue dot) after therapy (lower facet, below dashed line). Level of CMV reactivation is represented by the color of the circle as indicated in the legend with orange indicating CMV DNA qPCR ≥1,001, red indicating CMV DNA qPCR 401-1,000, and blue indicating CMV DNA qPCR ≤400. One patient (G) developed CMV enteritis which was diagnosed with a biopsy of the jejenum (yellow circled X) which demonstrated immunohistochemical staining for CMV in the context of xanthogranulomatous inflammation at day+31 after CAR T infusion. Time and duration of CMV treatment is indicated by the thicker horizontal black bar. Survival time of the patient is indicated by the narrower horizontal gray bar. The events for each patient have been recentered on the day of earliest CMV reactivation. ICANS: immune effector cell associated neurotoxicity syndrome; IU: international units; Rx: treatment; +: censored at last follow-up; x: disease relapse.