Blood cancer remission seen in patients given CAR-T immunotherapy

A new type of CAR-T immunotherapy that targets aggressive T-cell blood cancer shows high remission rates and manageable side effects, according to the results of an international clinical trial.

Traditionally, CAR-T immunotherapies are adapted from the patient's immune cells. These cells are then genetically modified to produce a protein on their surface called chimeric antigen receptors (CARs), which recognise and target cancer cells. Contrastingly, the therapy – WU-CART-007 – in clinical development is produced from cells donated from any healthy individual and can be used to treat any patient with a T-cell cancer. This deems the therapy universal and readily available, reducing the wait times before treatment.

'For patients with these rare and aggressive cancers, who have no other options, this has the potential to become a transformative advance in the field,' said Professor John DiPersio, director of the Centre for Gene and Cellular Immunotherapy at the Washington University School of Medicine, St Louis, Missouri, who first developed the therapy and senior author of the paper published in Blood. 'This CAR-T cell treatment shows promise in becoming a "bridge-to-transplant" therapy for patients who would otherwise not be eligible for stem cell transplantation, which is the only potentially curative treatment for these blood cancers.'

The clinical trial included 28 adult and adolescent participants with T cell acute lymphoblastic leukaemia and T cell lymphoblastic lymphoma that either returned after several lines of therapy or that standard therapy proved ineffective for them. This type of patient, on average, will only survive six months, and less than seven percent survive beyond five years.

The phase I/II clinical trial was conducted across multiple cancer centres in Europe, Australia and the USA. A dose escalation trial was performed on 15 patients, meaning patients were given increasing amounts of the new therapy to find the optimal dose. Subsequently, 13 patients were administered the full dose of 900 million CAR-T cells following lymphodepletion, a procedure that reduces the patients' immune cells to make room for the therapeutic cells. Two of these patients died from the cancer or treatment complications, such as infection, during the study period.

Among the 11 who completed the treatment, ten had their cancer disappear or significantly reduced, and eight were in complete remission, meaning they showed no evidence of cancer. At the study's data cut off, six patients who subsequently underwent a stem cell transplant remained in remission six to 12 months later.

'These responses are remarkable because the patients in this trial had run out of options. They had very aggressive cancers return after several lines of therapy, including several who relapsed after an earlier stem cell transplant,' said first and corresponding author Professor Armin Ghobadi, from the Washington University School of Medicine.

Nevertheless, the trial has revealed adverse effects of therapy, as 88.5 percent of patients experienced cytokine release syndrome, which is essentially full-body inflammation and a common side effect of CAR-T cell therapy. In addition, two patients experienced immune effector cell-associated neurotoxicity syndrome and one patient experienced mild graft-vs-host disease. The adverse events reported were all managed with additional therapies.

The researchers have launched a larger international clinical trial, with a longer follow-up, to further evaluate the therapy and to determine whether WU-CART-007 could be curative on its own.