Update on Monocentric CD19-CAR T-Cell Therapy in 30 Patients with Autoimmune Disease
Authors: Mueller Fabian , Hagen Melanie , Wirsching Andreas , Kharboutli Soraya , Spoerl Silvia , Tur Carlo , Krickau Tobias , Bucci Laura , Bergmann Christina , Auth Janina , Garantziotis Panayiotis , Boeltz Sebastian , Kretschmann Sascha , Vasova Ingrid , Mougiakakos Dimitrios , Aigner Michael , Grieshaber-Bouyer Ricardo , Metzler Markus , Voelkl Simon , Schett Georg , Mackensen Andreas 
Published: December 2024

Background: Treating autoimmune diseases (AID) like Systemic Lupus erythematosus (SLE), Idiopathic Inflammatory Myositis (IIM) or Systemic Sclerosis (SSc) is challenging and often requires life-long immunosuppressive therapy. In some patients, autoimmune disease progresses fast and leads to severe organ damage. Recent experience suggests that CD19-CAR T-cell therapy represents a potentially transformative new therapy approach achieving lasting, treatment-free remission in autoimmune diseases. Here we present an updated patient cohort of 30 patients with longer follow-up from a monocentric experience.

Methods: Patients with treatment-refractory, progressive systemic SLE (18 patients), SSc (7) and IIM (5) were treated with 1x106 /kg autologous 2nd generation CD19 CAR-T cells MB-CART19.1 produced in-house in a closed system. Patients were included in a named patient use program (N = 19) or in the monocentric CASTLE trial (N = 11) (EudraCT-No: 2022-001366-35). Before CAR T-cell infusion, lymphodepletion was infused with fludarabine (25 mg/m², d-5 to d-3) and cyclophosphamide (1000 mg/m², d-3). All immunosuppressive therapies were stopped at least two weeks prior to leukapheresis. A maximum of Prednisolone at 10 mg/day was allowed. Prevalence and severity of cytokine-release syndrome (CRS), immune effector cell-associated hematotoxicity (ICAHT), and immune effector cell-associated hematotoxicity (ICAHT) as well as the efficacy of CAR T-cell treatment was documented.

Results: The 30 patients including two pediatric SLE patients were treated between 2021 and May 2024. All patients showed uncontrolled, severe disease despite exposure to multiple drugs. Median follow-up was 12.5 months [range 1;39]. In the 26 patients with complete CAR T-cell involution (&lt; 1 cell/microliter), mean time of CAR T-cell presence was 47 days [range 16;100]. In the 23 patients with B-cell reconstitution, mean time of B-cell aplasia was 86 days [range: 30;196]. Patients developed only mild CRS (56,7% grade 1; 10% grade 2), one mild ICANS of grade 1 and no ICAHT. Infections were mild, mostly upper respiratory tract infections while 4 patients had an uncomplicated pneumonia after CD19-CAR T-cell treatment. Late neutropenia fullfilling ICHAT-citerea was observed in 4 patients with a median of 71 days [29-120] after CD19-CAR T-cell treatment and which was reverible upon short-term G-CSF treatment. In patients with at least 6-months follow-up (N=25), all SLE patients achieved DORIS remission, all myositis patients achieved 2016 ACR/EULAR major response and none of the SSc patients showed progression of interstitial lung disease (Table 1). Only one relapse with a milder myositis than at first CAR T treatment in an IIM patient was observed after 12 months of drug-free remission. All other 29 patients remain off their respective disease-specific therapy. An updated follow-up will be presented at the meeting.

Conclusion: Dynamics of CAR T-cell expansion, abrogation of most auto-antibodies, and reset of the B cell compartment are consistent among patients with three distinct AID. Tolerability has been high with no higher-grade acute toxicities and mild infectious complications in longer follow-up. Efficacy analysis showed long-standing drug-free remission (SLE and IIM) or no progression (SSc) with recurrence of disease in only one patient.