Needle in a haystack What T cell to target for #autoimmune diseases T cell repetoires (TCR) not all are sequenced and many can exist to present antigens Diff scales of approaches Implications CAR-T CD19 CD20 BCMA Treg HLAB27 etc! #ACR25 @ACRheum @RheumNow Alok Joglekar #26S08 https://t.co/Qgw8Akz1xk

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Prospective RCT on safety & efficacy of TAC+GC vs. MMF+GC TAC+GC was comparable to MMF+GC as continuous induction maintenance treatment over 96 wks for LN. AE rates comparable. TAC - AKI & tremor MMF - leucopenia reassuring data.more tx options. #ACR25 @RheumNow Abs2697 https://t.co/16Fd8zE5dL

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So what's been tried for ICANS, knowing that it's unlikely that one therapy will fix all of it? @CarolineDiorio @ChildrensPhila in the #ACR25 BCRC pre-meeting @RheumNow https://t.co/10wdkrH29s

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Toxicity is the big question about CAR-T in RA - what did the CRS/ICANS profile look like in this German ph1 in RA? Pretty good so far - but obviously will be under enormous scrutiny when we are looking at diseases with good existing therapies #ACR25 ABST0471 @RheumNow https://t.co/xXyzOwLvx8

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2465: Dual-target CD19/BCMA CAR-T in refractory SLE (Phase 1) 🔹All pts (n=10) met SRI-4 by wk24 🔹DORIS remission: 5 (wk24), 6 (wk36–48) 🔹Residual proteinuria (n=4); renal bx (n=3) showed resolved IC deposits & inflammation 🔹CRS Grade 1 (n=6); no ICANS @RheumNow #ACR25

What does the FDA regulatory approach look like for CAR-T and T cell engages right now? The FDA session at #ACR25 gave some clues @RheumNow https://t.co/wHNnNTrXaE

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LB23: Regulate-RA- ongoing Phase 1 trial of autologous CAR-Tregs in refractory RA (no lymphodepletion) 🔹 4/6 pts had ↓ DAS28-CRP by wk 4 with rapid onset & ↓ joint counts at dose level 2 🔹 Synovial biopsies to date showed ↓ inflammatory score post-tx @RheumNow #ACR25 https://t.co/JMBbLIEmJG

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LB04: Another approach to CAR-T, CD20+/BCMA bispecific CAR-T in refractory proliferative LN: 🔹100% discontinued biologics & IS at follow-up 🔹Renal response ~78% 🔹CRS mostly Grade 1–2 (~70%); ≥Grade 3 AEs = transient & hematologic @RheumNow #ACR25 https://t.co/oNK4wtLGYV

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#ACR25 Please find my blog on update and progress of clinical trials in #Sjogren #SjD @RheumNow https://t.co/u8pxZ5FeBX https://t.co/KAnRo3Zqnz

• Sjogren’s disease: two drugs with positive trials | RheumNow
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Abstract 1563: Ongoing Phase 1/2 trial of Rese-cel CAR-T in systemic sclerosis 🔹Pt with severe skin involvement showed improvement in mRSS (42→34), PFTs & nailfold capillaroscopy at 6 mo 🔹Grade 2 CRS, no ICANS or DLT reported Early but exciting findings @RheumNow #ACR25

While post-CAR-T CRS might be semi-familiar for rheumatologists, ICANS is a new concept to get our heads around, and one which is far from heterogenous. @CarolineDiorio @ChildrensPhila in the #ACR25 BCRC pre-meeting @RheumNow https://t.co/qX2jKMG2oB

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@CarolineDiorio @ChildrensPhila @RheumNow Indeed, there are a lot of familiar HLH/MAS friends in the post-CAR-T CRS mix... (indeed, rheum friends from many places) @CarolineDiorio @ChildrensPhila in the #ACR25 BCRC pre-meeting @RheumNow https://t.co/OzWu3MV1FA

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Another toxicity signal to watch in the CAR T space: LICATs Abstract 1537 reports a new immune-related toxicity distinct from CRS or ICANS: 🔹Affects organs prev involved in autoimmune dx: skin (35%) and kidneys (22%) 🔹Mostly mild (Grade 1–2); 3 cases Grade 3 @RheumNow #ACR25 https://t.co/mtZh47nWtv

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I've always (very) simplistically considered post-CAR-T CRS and HLH/MAS in the same bucket, and there certainly are substantial similarities. It raises the obvious question - can we borrow therapies? @CarolineDiorio @ChildrensPhila in the #ACR25 BCRC pre-meeting @RheumNow https://t.co/2HkHxpl89u

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What dictates how severe CRS is following CAR-T? (Often the critical question, and will especially be in the autoimmune space, where CAR-T is largely less time-critical) @CarolineDiorio @ChildrensPhila in the #ACR25 BCRC pre-meeting @RheumNow https://t.co/u0w4lx7YVn

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