REAL‐WORLD OUTCOMES OF INTRAVENOUS IMMUNOGLOBULIN FOR HYPOGAMMAGLOBULINEMIA AFTER CHIMERIC ANTIGEN RECEPTOR T‐CELL THERAPY IN PATIENTS WITH DIFFUSE LARGE B‐CELL LYMPHOMA

Abstract

Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy is a treatment for patients with diffuse large B-cell lymphoma (DLBCL) and is associated with toxicities, including hypogammaglobulinemia (HGG). Intravenous immunoglobulin (IVIG) is often used to manage HGG and prevent recurrent infections after CAR-T therapy, but more real-world evidence is needed to support this. Aim: To describe the real-world incidence of HGG and the effectiveness of IVIG after CAR-T therapy in patients with DLBCL. Methods: This observational cohort study used de-identified data from the nationwide (US-based) electronic health record (EHR)-derived Flatiron Health database. Patients were aged ≥18 years, diagnosed with DLBCL, had ≥2 visits in the Flatiron network on/after 1-Jan-11 and had received CAR-T therapy (tisagenlecleucel or axicabtagene ciloleucel) in any treatment line after 1-Jan-18. Baseline characteristics were identified in the 60 days prior to the index date (date of first CAR-T therapy administration). Outcomes, including HGG, were measured from index date until patient death or end of data availability (cut-off: 30-Apr-21). In this ad-hoc analysis, the primary objectives were to evaluate HGG incidence and IVIG use in patients with DLBCL who received CAR-T therapy. Exploratory objectives were to describe overall survival (OS) and progression-free survival (PFS) by IVIG treatment. Proportions and medians were used for patient characteristics. The Kaplan–Meier method was used for clinical outcomes. Results: Overall, 91 patients were included. During follow-up, 14 patients (15.4%) developed HGG, of which six cases were ‘directly attributed’ and one case ‘possibly attributed’ to CAR-T therapy; attribution was not documented for seven patients. Among these 14 patients, eight received treatment for HGG and six had no documented record of treatment. In total, 14/91 patients received IVIG (IVIG cohort). The IVIG cohort was younger (median [range] age 59 [32–67] vs 63 [28–83] years), had more females (50.0% vs 37.7%), had more patients with an Eastern Cooperative Oncology Group score of 2 (14.3% vs 6.5%) and was more frequently treated in a community setting (64.3% vs 49.4%) than the non-IVIG cohort. In the IVIG and non-IVIG cohorts, median (95% confidence interval [CI]) OS was not reached (NR; 5.6–NR) and 18.3 (9.1–NR) months, respectively and median (95% CI) PFS was NR (2.3–NR) and 3.0 (2.7–7.4) months, respectively. Conclusions: In this real-world study, half of the 14 HGG cases in patients with DLBCL were directly/possibly attributed to CAR-T therapy. This may be an underestimate because HGG is primarily assessed using laboratory data but here it was identified using EHRs. Despite a small sample size, the hypothesis-generating analyses of IVIG effectiveness and management outcomes support further evaluation of IVIG for the treatment of HGG in patients with DLBCL after CAR-T therapy. The research was funded by: Takeda Development Center Americas, Inc. Writing support was funded by: Takeda Pharmaceuticals International AG. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Immunotherapy Conflicts of interests pertinent to the abstract D. S. Chun Employment or leadership position: Takeda Development Center Americas, Inc. Stock ownership: Takeda Y. Yin Employment or leadership position: Takeda Development Center Americas, Inc. Stock ownership: Takeda C. Anderson-Smits Employment or leadership position: Takeda Development Center Americas, Inc. Stock ownership: Takeda