Survey of Infection Surveillance, Prophylaxis, and Vaccination Practices after Autologous Genetically Modified Cellular Therapies

Introduction Genetically modified cellular therapies (GMCT) using autologous hematopoietic stem cells are under investigation for various inherited disorders including inborn errors of immunity (IEI) and non-IEI indications. Disease and conditioning related defects in immunity vary across indications for GMCT and contribute to appropriate variations in practice. Nonetheless, evidence-based guidance for infection prevention is lacking. We sought to understand current practices around GMCTs from clinicians participating in GMCT clinical trials. Methods We identified individuals potentially experienced with GMCTs based on clinical trial participation on ClinicalTrials.GOV. After obtaining IRB approval electronic surveys were distributed via email. Results We approached 94 individuals in 11 countries. Seven of 21 responses for IEI and 19 of 25 for non-IEI from 6 countries (IEI: 3, non-IEI: 5) reported based on clinical experience with GMCTs. Figure 1 Surveillance All IEI GMCT respondents (n=7) reported standardized viral surveillance including weekly cytomegalovirus (CMV) monitoring (n=7), and regular Epstein-Barr virus (EBV) (n=6) and adenovirus (ADV) (n=5) monitoring. Some respondents also reported regular aspergillus antigen surveillance (n=4) and following IgG levels (n=5). Of the non-IEI GMCT respondents (n=19), CMV, EBV, and ADV were followed by 13, 12, and 9, respectively. Aspergillus antigen surveillance was not common practice (n=5). IgG levels were followed by 10 respondents. Table 1 Prophylaxis For IEI GMCT, all respondents reported use of Pneumocystis jirovecii (PJP) and fungal prophylaxis (ppx). Four reported using CMV ppx, 4 herpes simplex virus (HSV) ppx, and 3 varicella zoster virus (VZV) ppx. For non-IEI GCMT, use of ppx for PJP (n=18), fungus (n=15), and HSV (n=17) was common. Standard CMV and VZV ppx was infrequent. Encapsulated bacteria ppx was used by 11 respondents primarily for hemoglobinopathies (n=10). Table 2Preferred agent, and duration of ppx and surveillance were variable for both groups. Vaccination practices Most respondents acknowledge need for re-vaccination and use a universal protocol irrespective of pre-exiting immunity (IEI: 3, non-IEI: 9) or based on serology (IEI: 2; non-IEI: 7). Across both groups start of re-vaccination varied from 3 to 12 months after GMCT. Conclusion Reported infection prevention strategies are similar across respondents treating IEIs, but widely variable for non-IEI GMCT. Frequency and duration of monitoring and ppx were particularly inconsistent. Addressing re-vaccination is common albeit with variable implementation. Inherent variability and absence of evidence-based guidance has resulted in lack of standardization and difficulty in determining the ideal approach to infection protection. There is a need for development of rational guidelines based on harmonized assessment of risk after GMCTs.