Chimaeric antigen receptor (CAR) T-cell therapy is a type of cancer immunotherapy where patients’ T-cells are collected and genetically modified to produce chimaeric antigen receptors that recognise specific targets on cancer cells, allowing these T-cells to locate and destroy the cancer cells.

CAR T-cell therapy shows promising results in treating relapsing or refractory B-cell lymphomas.

To explore the risks associated with CAR T-cell therapy, researchers from Juntendo University, Japan, including Professor Jun Ando, Professor Miki Ando, and Dr. Erina Hosoya, published a study in Haematologica.

Elaborating about this study further, Dr. Hosoya, the study's lead author, says, “We conducted a single-centre, retrospective analysis of 59 patients with relapsed/refractory B-cell lymphoma enroled for CAR T-cell therapy with tisagenlecleucel (tisa-cel) between September 2020 and September 2023. Forty-one study patients (38 with diffuse large B-cell lymphoma (DLBCL) and three with follicular lymphoma (FL)) received an infusion of tisa-cel. Response assessments were completed in 37 patients with DLBCL and one with FL.” The team tracked overall survival (OS) and progress-free survival (PFS) over 12 months, finding OS at 73.8% and PFS at 49.6%.

Safety monitoring showed that 30 out of 41 patients who received tisa-cel developed cytokine release syndrome (CRS), an inflammatory side effect.

Of these, 14 patients had more severe CRS (grade 3 or higher) and also tended to receive higher doses of CAR-positive cells, leading to earlier fevers compared to those with milder (grade 1 or 2) CRS.

The researchers identified 11 laryngeal oedemas in patients as a serious and previously unrecognised side effect of CAR T-cell therapy.

Initially thought to affect only those with neck tumours, it was found in all patients, regardless of tumour location.

Intensive care and airway management were provided due to the obstruction caused by the oedema.

This condition typically developed within 3.4 days post-infusion and resolved within 14 days for all patients.

Explaining these results, Dr. Hosoya says, “Although a few case reports of laryngeal oedema with tisa-cel treatment for B-cell lymphoma have appeared, the mechanism of this phenomenon is still unknown and no established management guidelines exist despite the major risk of life-threatening airway obstruction. We, therefore, assessed risk factors for the occurrence of laryngeal oedema and the influence of steroid treatment on both CAR T-cell expansion and clinical outcome.” The research team identified a key risk factor for laryngeal oedema—patients who experienced this condition had a significantly higher number of CAR-positive cells infused (4.0 x 10⁸ vs 3.3 x 10⁸).

They found that infusions with more than 3.4 x 10⁸ CAR-positive cells could predict the risk of laryngeal oedema.

Additionally, the CAR T-cells from patients with laryngeal oedema contained a higher proportion of effector T-cells compared to those without oedema.

Sharing another interesting observation from the study, Dr. Hosoya says, “Our impression clinically was that the frequency of laryngeal oedema after tisa-cel infusion rose in the summer of 2022. So, we attempted to coordinate the date of tisa-cel manufacture with the occurrence of laryngeal oedema.” This observation was a result of the high numbers of CAR-positive cells in products manufactured after June 2022 than in those manufactured before June 2022.

Based on these observations from the study, the team of researchers concludes that using steroids, such as dexamethasone, could prove effective for early management of laryngeal oedema.

They found that administering steroids provided relief to patients without reducing the effectiveness of CAR T-cell therapy.

In summary, these findings highlight the serious adverse effects of tisa-cel therapy, its associated risk factors, and management strategies for improving patient safety and treatment experiences.

Concluding optimistically, Dr. Hosoya says, “We believe that our analyses encompass both efficacy and safety with tisa-cel therapy in real-world settings.”

Source: Juntendo University Research Promotion Center