
Markus Eckstein: Only the CAR-T Cohort Achieved Drug-free Remission at 3 months
Markus Eckstein, Advanced Clinician Scientist at the IZKF, shared a post on X:
“Sequential inguinal-LN biopsies in 24 patients with SLE, SSc, RA and IIM reveal that a single infusion of CD19-CAR-T cells eradicates intranodal CD19/20⁺ B cells (0 cells mm-² in all 12 cases) and collapses germinal-centre architecture (FDC-, TFH- and Ki-67-negative).
By contrast, next-gen protein therapies – obinutuzumab (-92 % CD20⁺), rituximab (-86 %) and blinatumomab (-69 %) – leave residual follicles and plasmablast/plasma-cell niches. Only the CAR-T cohort achieved drug-free remission at 3 months, underscoring that depth and anatomical locus of B-cell depletion, not peripheral counts alone, dictate durable disease control.
24 autoimmune pts (SLE, SSc, RA, IIM): OBI n=4, BLI n=4, RTX n=4, CD19-CAR-T n=12. Inguinal LN biopsies pre-tx & 30–86 d later (peripheral B=0). IHC for CD19/20, plasma cells, FDC, TFH, Ki-67, CD3, CD68.
In-node B-cell change (CD20): CAR-T 100 % clearance → OBI –92 % → RTX –86 % → BLI –69 %. Only CAR-T drove CD19/CD20 to 0 cells mm-² in every patient. Peripheral counts alone overestimate response!
Follicular architecture: CAR-T obliterated germinal centres—FDC network gone, TFH absent, Ki-67 low (median score 0/8). Protein drugs kept residual follicles (median 4–6). Deep depletion = GC collapse.
Plasma cells persisted in all arms, but CAR-T cut CD19⁺CD138⁺ plasmablasts by 59 %. CD3⁺ T cells & CD68⁺ macrophages stayed stable—showing a precise B-cell hit, not wholesale tissue damage.
Outcomes: All 12 CAR-T pts in drug-free remission at 3 mo; protein-treated pts needed retreatment despite peripheral aplasia. Lesson: depth and location of depletion matter—CAR-T sets the benchmark for future B-cell therapeutics.”
Read more.
Title: Effects of different B-cell-depleting strategies on the lymphatic tissue
Authors: Carlo Tur, Markus Eckstein, Laura Bucci, Janina Auth, Christina Bergmann, Simon Rauber, Melanie Hagen, Danae-Mona Nöthling, Sebastian Böltz, Andreas Wirsching, Koray Tascilar, Filippo Fagni, Giulia Corte, Aleix Rius Rigau, Yi Qin, Panagiotis Garantziotis, Jule Taubmann, Jochen Wacker, Andreas Ramming, Maria Antonietta D’Agostino, Sebastian Rauch, Arndt Hartmann, Fabian Müller, Andreas Mackensen, Ricardo Grieshaber-Bouyer, Georg Schett, Aline Bozec, Maria Gabriella Raimondo
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