CD19-targeted chimeric antigen receptor T-cell therapy in patients with concurrent B-cell Non-Hodgkin lymphoma and rheumatic autoimmune diseases: a propensity score matching study.

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.

Real-world evidence of incidence and outcomes of aplastic anaemia following administration of immune checkpoint inhibitors.

Aplastic anaemia (AA) is a rare immune-related adverse events (irAEs) after immune checkpoint inhibitors (ICIs) administration with poorly understood incidence and outcomes. We analysed an electronic health record database of 52 303 ICI-treated patients and found 77 (0.15%) cases of AA, with a median onset of 126 days (interquartile range, 58-363 days). The most used treatment for AA was systemic glucocorticoids 60 (77.9%) and 32 (41.6%) patients were able to resume ICI within 1 year. Patients diagnosed with AA had a steep decline in overall survival (OS) within the first 120 days; when compared to propensity score-matched patients without AA, they had a significantly worse OS (hazard ratio 1.72, 95% confidence interval 1.19-2.50; p = 0.003).

Early versus late response to daratumumab-based triplet therapies in patients with multiple myeloma: a pooled analysis of trials POLLUX, CASTOR and MAIA.

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.