CAR-T Cytokine Release Syndrome Shows Distinct Symptom Profiles by Timing, Severity and Duration

Patients with relapsed or refractory multiple myeloma who receive CAR-T-cell therapy frequently develop cytokine release syndrome (CRS), a systemic inflammatory complication that can range from fever and chills to life-threatening low blood pressure. A retrospective observational study now reports that the clinical picture of CRS differs systematically depending on when it begins, how severe it becomes and how long it lasts, offering clinicians a framework for earlier recognition and symptom-directed monitoring.

The study, published in BMC Cancer, analysed data from 128 patients with relapsed/refractory multiple myeloma who had been treated with CAR-T-cell therapy. The researchers collected demographic information, haematological indicators and clinical manifestations, and stratified CRS into subgroups along three binary clinical dimensions: onset timing, severity and duration. Categorical variables were reported as counts and percentages, continuous variables as means with standard deviations or medians with interquartile ranges, and groups were compared using the Mann-Whitney U test and the chi-square test.

Across the cohort, the most common manifestations of CRS were high fever, recorded in 86.72% of patients, chills in 85.16%, tachycardia in 83.59%, sweating in 79.69%, mucocutaneous pallor in 75.78% and fatigue in 75%.

The subgroup comparisons revealed statistically significant differences. Patients whose CRS began immediately had a lower rate of mucocutaneous pallor than those with non-immediate onset, at 61.4% versus 87.32% (p = 0.001). When severity was considered, severe CRS was associated with a higher incidence of high fever than mild CRS (95.74% versus 81.48%, p = 0.022), as well as more frequent chest tightness (31.91% versus 13.58%, p = 0.013) and dyspnoea (42.55% versus 17.28%, p = 0.002). Duration also mattered: patients with persistent CRS showed a lower incidence of significant hypotension than those with non-persistent CRS, at 22.7% versus 40.0% (p = 0.044).

These associations suggest that specific symptoms may serve as markers of CRS subtype. Respiratory complaints such as chest tightness and dyspnoea clustered with severe episodes, while pallor distinguished immediate from delayed onset. The authors conclude that the clinical manifestations of CRS are closely associated with its onset timing, duration and severity, and that distinct symptom profiles across subgroups support tailored nursing surveillance and intervention to optimise patient outcomes.

The findings come against the backdrop of CAR-T therapy’s remarkable efficacy in relapsed/refractory multiple myeloma, where treatment-related complications, particularly CRS, have emerged as major barriers to wider application. CRS produces a wide range of clinical symptoms and can induce severe systemic inflammation, which in turn can result in treatment failure and even death. Characterising how presentations differ across CRS subgroups is therefore intended to inform early recognition and individualised, symptom-directed management.

Several limitations of the study design should be kept in view. It was retrospective and observational, based on a single cohort of 128 patients, and the reported associations are cross-sectional comparisons rather than evidence that any symptom predicts a particular CRS course prospectively. The authors also note that because the work was non-interventional, clinical trial registration was not required and the study was not registered in any clinical trial registry. The article was shared early as a peer-reviewed, accepted version of record pending final edits.

Even so, the study provides a structured, quantified description of how CRS looks in practice across timing, severity and duration strata. For clinicians and nursing teams managing patients after CAR-T infusion, the message is that a single uniform checklist of CRS symptoms may be insufficient: the presence or absence of pallor, respiratory symptoms or significant hypotension may carry different implications depending on the subgroup a patient falls into.

Subject of Research: Clinical manifestations of cytokine release syndrome subgroups in relapsed/refractory multiple myeloma patients treated with CAR-T-cell therapy

Article Title: Analysis of different types of cytokine release syndrome in patients with relapsed/refractory multiple myeloma: a retrospective study

Article References: Chen, L., Cheng, Y., Yan, J., Wang, Z., Cai, L., Cheng, Q., Zhou, X., Feng, J., & Ding, S. (2026). Analysis of different types of cytokine release syndrome in patients with relapsed/refractory multiple myeloma: a retrospective study. BMC Cancer. https://doi.org/10.1186/s12885-026-17243-0

Image Credits: AI Generated

DOI: 10.1186/s12885-026-17243-0

Keywords: CAR-T therapy, cytokine release syndrome, multiple myeloma, relapsed/refractory, retrospective study, CRS severity, onset timing, CRS duration, hypotension, dyspnoea, nursing surveillance, BMC Cancer