Toxicities, intensive care management, and outcome of chimeric antigen receptor T cells in adults: an update.

BACKGROUND: Chimeric antigen receptor T cells are a promising new immunotherapy for haematological malignancies. Six CAR-T cells products are currently available for adult patients with refractory or relapsed high-grade B cell malignancies, but they are associated with severe life-threatening toxicities and side effects that may require admission to ICU. OBJECTIVE: The aim of this short pragmatic review is to synthesize for intensivists the knowledge on CAR-T cell therapy with emphasis on CAR-T cell-induced toxicities and ICU management of complications according to international recommendations, outcomes and future issues.

Calibration trial of an innovative medical device (NEVVA© ) for the evaluation of pain in non-communicating patients in the intensive care unit.

Background: Pain management is an essential and complex issue for non-communicative patients undergoing sedation in the intensive care unit (ICU). The Behavioral Pain Scale (BPS), although not perfect for assessing behavioral pain, is the gold standard based partly on clinical facial expression. NEVVA© , an automatic pain assessment tool based on facial expressions in critically ill patients, is a much-needed innovative medical device. Methods: In this prospective pilot study, we recorded the facial expressions of critically ill patients in the medical ICU of Caen University Hospital using the iPhone and Smart Motion Tracking System (SMTS) software with the Facial Action Coding System (FACS) to measure human facial expressions metrically during sedation weaning. Analyses were recorded continuously, and BPS scores were collected hourly over two 8 h periods per day for 3 consecutive days. For this first stage, calibration of the innovative NEVVA© medical device algorithm was obtained by comparison with the reference pain scale (BPS). Results: Thirty participants were enrolled between March and July 2022. To assess the acute severity of illness, the Sequential Organ Failure Assessment (SOFA) and the Simplified Acute Physiology Score (SAPS II) were recorded on ICU admission and were 9 and 47, respectively. All participants had deep sedation, assessed by a Richmond Agitation and Sedation scale (RASS) score of less than or equal to -4 at the time of inclusion. One thousand and six BPS recordings were obtained, and 130 recordings were retained for final calibration: 108 BPS recordings corresponding to the absence of pain and 22 BPS recordings corresponding to the presence of pain. Due to the small size of the dataset, a leave-one-subject-out cross-validation (LOSO-CV) strategy was performed, and the training results obtained the receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.792. This model has a sensitivity of 81.8% and a specificity of 72.2%. Conclusion: This pilot study calibrated the NEVVA© medical device and showed the feasibility of continuous facial expression analysis for pain monitoring in ICU patients. The next step will be to correlate this device with the BPS scale.

Salvage therapy with brentuximab-vedotin and bendamustine for patients with R/R PTCL: a retrospective study from the LYSA group.

Patients with relapsed or refractory (R/R) peripheral T-cell lymphomas (PTCL) have a poor prognosis. Bendamustine (B) and brentuximab-vedotin (Bv) have shown interesting results in this setting. However, little information is available about their efficacy in combination. This multicenter and retrospective study aimed to evaluate the efficacy and safety of the combination of BBv in patients with noncutaneous R/R PTCL among 21 LYSA centers in France and Belgium. The primary objective was the overall response rate. A total of 82 patients with R/R PTCL were included. The best overall response rate (ORR) was 68%, with 49% of patients in complete response (CR). In multivariable analysis, only the disease status after the last regimen (relapse vs refractory) was associated with the response with an ORR of 83% vs 57%. Median duration of response was 15.4 months for patients in CR. With a median follow-up of 22 months, the median progression free survival (PFS) and overall survival (OS) were 8.3 and 26.3 months respectively. Moreover, patients in CR, who underwent an allogeneic transplant, had a better outcome than patients who did not with a median PFS and OS of 19.3 vs 4.8 months and not reached vs 12.4 months, respectively. Fifty-nine percent of patients experienced grade 3/4 adverse events that were mainly hematologic. BBv is highly active in patients with R/R PTCL and should be considered as a one of the best options of immunochemotherapy salvage combination in this setting and particularly as a bridge to allogeneic transplant for eligible patients.