John: Hello, I'm John Hilton, senior editor at Cochrane. Diffuse large B-cell lymphoma is a fast-growing cancer of the lymphatic system. A new Cochrane Review from September 2021 looks at the evidence on the effects of one treatment, chimeric antigen receptor (CAR) T-cell therapy for people whose disease relapses or does not respond to other treatments. We asked the lead author, Moritz Ernst from the Faculty of Medicine and University Hospital Cologne in Germany to tell us what they found.

Moritz: Diffuse large B-cell lymphoma, or DLBCL, affects blood cells that produce antibodies to fight infections. It is potentially curable, and most patients respond well to initial therapies such as chemotherapy but, for some, the disease becomes refractory or relapses. At that time, some patients receive chemotherapy and stem cell transplantation, but not all patients are eligible for this treatment; and, of those who are eligible, around half will experience relapse after it.
Patients who relapse or are refractory to advanced lines of treatment and those who are not eligible for a stem cell transplant have very poor prognosis, with only half of them surviving longer than 6 to 12 months. A new treatment for these people is called CAR T-cell therapy, which uses the body's own T-cells, which are immune cells, to fight DLBCL. In CAR T-cell therapy, T-cells are first removed from the patient's blood, equipped with so-called 'chimeric antigen receptors' (CARs) that help to recognise and destroy the cancer cells, and then delivered back into the patient's blood.
In our review, we wanted to provide a comprehensive overview of the potential benefits and harms of CAR-T cell therapy for people with relapsed or refractory DLBCL. We searched for studies available up to September 2020 but found no data from randomized trials or other trials with a control group. Instead, we found data from 13 uncontrolled studies with information on 679 participants and this means that the evidence is very uncertain for the outcomes we were interested in: overall survival, quality of life, and adverse events. We also identified 38 ongoing trials.
Considering the outcomes for patients, in four studies included in our review, half the participants survived longer than 12 months and quality of life improved over time in two included studies. When it comes to safety, almost all patients in five studies experienced some kind of adverse event and many of these patients experienced severe adverse events. For example, more than half the participants in three studies experienced serious adverse events and, in five studies, between half and all patients experienced cytokine release syndrome, an overreaction of the immune system that is typically seen after CAR-T cell therapy.
We also examined disease progression and response to treatment and found that between 40 and 75% of patients did not progress after 12 months in 4 studies, while, in 3 studies, 40-45% had a complete response.
In summary, these results indicate a potential of CAR-T cell therapy to improve outcomes for this population with an otherwise poor prognosis. However, as I pointed out, the evidence is very uncertain, mainly because of the lack of direct comparisons of CAR-T cell therapy with other treatments. Moreover, the potential harms of this therapy should not be neglected as patients often require additional treatments for the management of complications such as cytokine release syndrome.
To conclude, information from the studies that were available in September 2020 inidcates that we remain uncertain about the potential of CAR T-cell therapy to treat people with relapsed or refractory DLBCL. Therefore, conclusions based on our current results should be drawn very carefully and potentially revised when new evidence becomes available. Some of this may come next year, from three large ongoing trials comparing CAR T-cell therapy versus standard care and we will update our review to take account of that data.

John: If you'd like to read the current review and watch for future updates as new evidence becomes available, the review is available online. Just go to Cochrane Library dot com and search 'CAR-T cell therapy'.