In response to: “Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee” by Greco et al.

We would like to highlight four points regarding recent EBMT recommendations for the use of chimeric antigen receptor (CAR) T cells in autoimmune diseases.1 First, the recommendations are based on conventional, integrating vector-based CAR-Ts, which require lymphodepletion chemotherapy, inpatient administration and prolonged post-infusion monitoring. In phase 1/2 trials in generalized myasthenia gravis, mRNA CAR-Ts were administered outpatient, without lymphodepletion, and resulted in no cytokine release syndrome or neurotoxicity.2 Different monitoring recommendations are needed for mRNA CAR-T and other cellular therapies associated with an improved safety profile. Second, “stable disease” is noted as a contraindication for administering cellular therapy in patients with neurologic autoimmune disease, in contrast to the statement that advanced cell therapies should be considered “in case of fluctuating or inadequate clinical response to second-line immunosuppressive treatment”. While we agree with the latter phrasing, the common meaning of “stable disease” implies unchanged symptoms over time regardless of severity. The term should thus be clearly defined or reconsidered. Third, many specialties have already defined criteria for what constitutes meaningful response and unacceptable toxicity. For example, International Consensus Guidelines for myasthenia gravis emphasize that medication side effects should be no greater than grade 1.3 These considerations should be integrated for each specialty. Lastly, the referenced methodology by the EBMT practice harmonization and guidelines committee4 does not state which if any consensus methodology was used (e.g., modified Delphi appropriateness method).5 As the recommendations affect many stakeholders across several disciplines, the method by which inter and intra-disciplinary consensus was reached should be clarified.