P1413: does tocilizumab increase the risk of infections in patients undergoing car-t therapy?

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising treatment option for patients with relapsed/refractory large B-cell lymphoma (LBCL). Axicabtagene ciloleucel (Yescarta®) and Tisagenlecleucel (Kymriah®) received interim commissioning for this indication in early 2019 in the UK. Their use is associated with a number of adverse events, including cytokine release syndrome (CRS) and neurotoxicity. Tocilizumab, a monoclonal antibody that blocks the interleukin-6 receptor, has been widely used in high doses to manage CRS. More recently, there has been growing concern that high dose Tocilizumab may increase the risk of infections post-CAR-T treatment. In this single-centre retrospective study we investigate the impact of Tocilizumab on the rate of infections at 30 and 90 days post CAR-T therapy. Aims: To investigate the impact of Tocilizumab on post CAR-T 30- & 90-days infection risk. Methods: All adult patients undergoing CAR-T therapy at Manchester Royal Infirmary, UK, between May 1st 2019 and April 30th 2022 were included. Patients were split into two cohorts based on the number of Tocilizumab doses they received; Cohort A included patients who received no or one dose of Tocilizumab, while cohort B included patients who received 2 to 4 doses of Tocilizumab. Documented bacterial, viral and fungal infections diagnosed with positive cultures, positive fungal biomarkers, viral PCR tests or respiratory viral swabs over a 90-day period were recorded along with clear radiological evidence of infection on CT chest but no confirmed organism. Results: A total of 61 patients underwent CAR-T therapy with one of the two commissioned products during this 3-year period. Twenty-one patients were in cohort A with a median age of 51.5 years (range 30-73) and 40 patients were assigned to cohort B with a median age of 48 years (range 20-76). Out of the 61 documented infective episodes, 19 were found in cohort A and 42 in cohort B. In both cohorts, around 75% (74-79%) of infections occurred within the first month of CAR-T infusion. In cohort A, there were 7 bacterial (UTI, atypical mycobacterium, infective diarrhea), 7 viral (CMV, BK/JC,HHV6 &Rhinovirus), no fungal infections and 5 chest infections based solely on radiological changes. In cohort B there were 15 bacterial (Blood stream infection, infective diarrhea & UTI), 14 viral (EBV, CMV, BK/JC reactivations, respiratory viruses, Noro virus and Adeno virus), 5 fungal (3 candidaemias, 2 aspergillosis) and 8 radiological chest infections, respectively. In cohort B, 22 (55%) patients received concurrent steroids compared to only 4 (19%) in cohort A. - Demographic Total Group A 0-1 Doses of Tocilizumab Group B 2-4 Doses of Tocilizumab Patients (n) 61 21 40 Median age at CAR-T infusion (years, range) 51.5 (30-73) 48 (20-76) Male 32 14 (67%) 18 (45%) ProductAxicabtagene ciloleucel (Yescarta®)Tisagenlecleucel (Kymriah®) 4615 156 319 Concurrent steroids 26 4 (19%) 22 (55%) InfectionsTotal (n)Month 1 6146 (75.4%) 1915 (78.9) 4231 (73.8%) Blood stream infection 0 8 Other Bacterial infections. 7 7 Viral reactivations 4 8 Other viral infection(respiratory, GI Viruses) 3 6 Fungal 0 5 Other 5 8 Summary/Conclusion: Risk of infection post CAR-T is significantly higher in the first 30 days regardless of the amount of Tocilizumab administration, with the infection risk reducing nearly 3 times thereafter. In our retrospective study Tocilizumab treatment does not increase the risk for bacterial or viral infections, however, there is a trend to more fungal infections in patients receiving repeated doses of Tocilizumab. More studies with larger patient numbers are needed to investigate this further. Keywords: Infection, Lymphoma, CAR-T