GLA/DRST real-world outcome analysis of CAR T-cell therapies for large B-cell lymphoma in Germany.
Wolfgang Andreas BethgePeter MartusMichael SchmittUdo HoltickMarion SubkleweBastian von TresckowFrancis AyukEva Maria Wagner-DrouetGerald G WulfReinhard MarksOlaf PenackUlf SchnetzkeChristian KoeneckeMalte von BoninMatthias StelljesBertram GlassClaudia D BaldusVladan VucinicDimitrios MougiakakosMax ToppMatthias A FanteRoland SchroersLale BayirPeter BorchmannVeit L BückleinJustin HasenkampChristine HanounSimone ThomasDietrich W BeelenClaudia LengerkeNicolaus KroegerPeter DregerPublished in: Blood (2022)
CD19-directed chimeric antigen receptor (CAR) T cells have evolved as a new standard-of-care (SOC) treatment in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). Here, we report the first German real-world data on SOC CAR T-cell therapies with the aim to explore risk factors associated with outcomes. Patients who received SOC axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) for LBCL and were registered with the German Registry for Stem Cell Transplantation (DRST) were eligible. The main outcomes analyzed were toxicities, response, overall survival (OS), and progression-free survival (PFS). We report 356 patients who received axi-cel (n = 173) or tisa-cel (n = 183) between November 2018 and April 2021 at 21 German centers. Whereas the axi-cel and tisa-cel cohorts were comparable for age, sex, lactate dehydrogenase (LDH), international prognostic index (IPI), and pretreatment, the tisa-cel group comprised significantly more patients with poor performance status, ineligibility for ZUMA-1, and the need for bridging, respectively. With a median follow-up of 11 months, Kaplan-Meier estimates of OS, PFS, and nonrelapse mortality (NRM) 12 months after dosing were 52%, 30%, and 6%, respectively. While NRM was largely driven by infections subsequent to prolonged neutropenia and/or severe neurotoxicity and significantly higher with axi-cel, significant risk factors for PFS on the multivariate analysis included bridging failure, elevated LDH, age, and tisa-cel use. In conclusion, this study suggests that important outcome determinants of CD19-directed CAR T-cell treatment of LBCL in the real-world setting are bridging success, CAR-T product selection, LDH, and the absence of prolonged neutropenia and/or severe neurotoxicity. These findings may have implications for designing risk-adapted CAR T-cell therapy strategies.
Keyphrases
- stem cell transplantation
- cell therapy
- free survival
- diffuse large b cell lymphoma
- healthcare
- stem cells
- high dose
- acute lymphoblastic leukemia
- acute myeloid leukemia
- palliative care
- bone marrow
- coronary artery disease
- metabolic syndrome
- cardiovascular events
- cardiovascular disease
- skeletal muscle
- replacement therapy
- smoking cessation
- pain management
- glycemic control
- health insurance
- insulin resistance