Chimeric antigen receptor T (CAR-T) cells have shown promising results in treating patients with relapsed/refractory (R/R) B cell malignancies. With the recent approval of both axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisagen) for the treatment of R/R high-grade B non-Hodgkin lymphoma (NHL), we see more patients being referred for this novel therapy. There have been some published data looking at short- and long-term infection risks with this therapy and hypogammaglobulinaemia associated with B cell aplasia.1,2
We look at our cohort of patients being treated at Kings College Hospital with Axi-cel or Tisagen for R/R NHL to identify our incidence of short- and long-term infections and to identify risk factors that may contribute.
We collected our single centre's data on patients treated with CD19 CAR-T cells from Jan-Aug 2019. Eligibility is determined independently by a panel of clinical experts from NHS England and clinical data collected prospectively.
A total of 31 patients were treated with axi-cel and 3 patients with tisagen during this period. All developed neutropenic fevers with at least Grade 1 cytokine release syndrome (CRS). A total of 26 patients required tocilizumab for CRS and 12 patients needed steroids for Grade 2 CRS unresponsive to tocilizumab. 3 patients had positive blood cultures within the first 28 days of CAR-T infusion and only 1 patient required treatment for proven fungal chest at D28. In regards to late infections, one patient had pneumocystis pneumonia at 6 months and another had line associated acinetobacter sepsis at 2 months in the setting of persistent neutropenia. 8 patients had positive respiratory viruses with 5 achieving lymphocyte recovery post CAR-T. 25 patients had B cell aplasia pre-CAR-T therapy and by 1 month nearly all patients had B cell aplasia. Pre-CAR-T 10 patients had IgG levels < 4g/L with 2 having regular immunoglobulin replacement prior and at 1-month post treatment 14 patients had levels < 4g/L. 2 patients required regular immunoglobulin replacement post CAR-T; one was for bronchiectasis. The other patient had significant infections within the first 100 days, this included HHV6 encephalitis, recurrent E. coli UTIs, Kliebsiella bacteraemia and pneumonia; he was treated with antibiotics as well as immunoglobulin replacement. One patient in remission died suddenly in their local hospital of sepsis at 7 months. All patients had routine prophylaxis with aciclovir, co-trimoxazole and fluconazole; patients were changed over to posaconazole as per hospital policy if evidence of prolonged neutropenia.
In our cohort most patients treated with CAR-T cells did not appear to have an increased risk of early or late infections and this is despite CRS and administration of tocilizumab and steroids. There was 1 patient who had significant infections post CAR-T likely due to persistent neutropenia and lymphopenia and another who died of late sepsis. Despite significant B cell aplasia pre and post CAR-T the immunoglobulin levels in most patients remained >4g/L which suggests that the humoral immune system can remain intact despite B cell aplasia. Immunoglobulin levels will be correlated with 6-month outcomes in final analysis.
Nothing to declare