RESUMO
Rheumatic autoimmune diseases not only involve the production of autoantibodies but also demonstrate T-cell dysfunction. In patients with concurrent B-cell non-Hodgkin lymphoma (NHL) and rheumatic autoimmune diseases, the safety and efficacy of CD19-targeted chimeric antigen receptor (CAR) T-cell therapy are unknown. Using an aggregated electronic health record database, patients with rheumatic autoimmune diseases (auto group) were compared to propensity score-matched patients without rheumatic autoimmune diseases (non-auto group). From 1/2019 to 1/2023, 58 (4.3%) of 1,363 patients who received CD19-targeted CAR T-cell therapy had concurrent rheumatic autoimmune diseases. Both groups had similar incidence, severity, and management of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Moreover, the two groups had similar time-to-next treatment or death (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.60 to 1.59, log-rank p = 0.91) and overall survival (HR 0.90, 95%CI 0.46 to 1.78, p = 0.76). Following CAR T-cell infusion, patients with rheumatic autoimmune diseases achieved decreased inflammatory markers, seronegative conversion of autoantibodies, as well as reduced use of steroids and disease-modifying anti-rheumatic drugs. In conclusion, the safety and efficacy of CAR T-cell therapy were not affected in patients with rheumatic autoimmune diseases. Moreover, they achieved better biochemical control of underlying rheumatic diseases.
Assuntos
Doenças Autoimunes , Linfoma não Hodgkin , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/efeitos adversos , Receptores de Antígenos de Linfócitos T , Pontuação de Propensão , Antígenos CD19 , Linfoma não Hodgkin/terapia , Doenças Autoimunes/terapia , Doenças Autoimunes/etiologia , Autoanticorpos , Terapia Baseada em Transplante de Células e TecidosAssuntos
Carcinoma Pulmonar de Células não Pequenas , Falência Renal Crônica , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico , Falência Renal Crônica/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Estudos RetrospectivosRESUMO
In multiple myeloma (MM), it is unclear whether early and late responders to daratumumab have similar outcomes. We pooled individual-level data from phase 3 trials and divided them into early and late response groups based on median time to response. Altogether 670 and 213 patients achieved very good partial response (VGPR) or better and minimal residual disease (MRD) negativity, respectively. Among VGPR or better, there was no significant difference of modified progression-free survival (mPFS, hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.69-1.44) or duration of response (DOR) (HR 1.02, 95%CI 0.68-1.53). Among relapsed/refractory MM (RRMM) achieving MRD negativity, late responders had significantly longer mPFS (p = 0.038) and DOR (p = 0.043). These results support that for patients who failed to achieve an early response to daratumumab, therapies should be continued with the goal of achieving ongoing and stepwise improvement of response.