Abstract

• Patients with relapsed or refractory diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, after several lines of therapy, have a poor prognosis. As of mid-2019, there is no consensus on subsequent treatment. Chemotherapy is sometimes offered, but it has not been shown to extend survival more than appropriate symptomatic care.
   
• Axicabtagene ciloleucel (Kite Pharma) is a CAR (chimeric antigen receptor) T-cell therapy. Treatment entails harvesting T cells from the patient, sending them to a manufacturing centre where they are genetically modified to express a chimeric receptor on their surface that recognises CD19 (an antigen present on the surface of the neoplastic and other B cells), then infusing the modified T cells into the patient.
   
• Axicabtagene ciloleucel has been authorised in the European Union to treat adults with diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, after failure of at least two lines of therapy.
   
• In this situation, axicabtagene ciloleucel has been evaluated in a single non-comparative trial in 111 patients whose disease relapsed after at least two lines of therapy or an autologous haemopoietic stem cell transplant. After a median follow-up of 2 months, it was estimated that 51% of patients were still alive after 2 years. This result is superior to that reported for a retrospective cohort of 636 patients who had received conventional treatments and had a median survival of 6 months. The evidence provided by such indirect comparisons is considered weak.
   
• All patients treated with axicabtagene ciloleucel experienced adverse effects, and half of them had serious adverse effects. In particular, almost all patients developed cytokine release syndrome and neurological disorders (including encephalopathy). Other notable adverse effects were infections and haematological disorders. Some patients died of an adverse effect related to their CAR T-cell therapy.
   
• There are several stages to the axicabtagene ciloleucel treatment protocol. The lengthy production process restricts this treatment to patients whose disease is not likely to worsen before the modified T cells are ready. One inconvenience is that patients are advised to remain close to a certified centre authorised to conduct CAR T-cell therapy for at least 4 weeks, in case serious adverse effects occur. 
   
•  OFFERS AN ADVANTAGE  For patients with large B-cell lymphoma or mediastinal lymphoma, one non-comparative trial in 111 patients who had exhausted all other treatment options showed that half of the patients were still alive about two years after infusion of axicabtagene ciloleucel, a therapy based on genetically modified T cells. The magnitude of this benefit is difficult to determine because it is based on weak evidence from comparison with a historical control group, in which median survival with other treatments was 6 months. Axicabtagene ciloleucel provokes a great many adverse effects that are often serious or even fatal. The treatment procedure is burdensome and inconvenient, and mainly suited to patients who are otherwise well. In summary, there is a pressing need for more thorough clinical evaluation of this CAR T-cell therapy.

©Prescrire 1 Octrober 2019

"Axicabtagene ciloleucel (Yescarta°) in certain types of lymphoma when other treatment options have been exhausted" Prescrire Int 2019; 28 (208): 229-231. (Pdf, subscribers only).

Share