NextGen 2024: Bone Marrow Transplantation (BMT) Session Part 4

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Key Insights

A study of 31 patients with severe, refractory juvenile idiopathic arthritis (JIA) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) between 2007 and 2022.
75% of the initial cohort of 16 patients achieved complete remission (CR).
The 6-year overall survival (OS) rate for the updated cohort of 31 patients was 84%.
Relapse occurred in 42% of patients, and transplant-related deaths occurred in 4x of cases.
Allogeneic HSCT presents a viable option for patients with refractory and/or complicated sJIA, showing promising results for Interstitial Lung Disease(ILD).

#sjiafoundation #sjia #bmt #curesjia

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1. Long Term outcomes of Allogeneic HSCT for severe, refractory Juvenile Idiopathic Arthritis Juliana Silva Bone marrow Transplant Consultant Great Ormond Street Hospital London, UK

2. Allo-HSCT for JIA • Most common cancer in children & most common cause of death < 20 years of age; • 16 patients underwent allo HSCT from 5 different centres • Median FU was 2y 5m • 4 MSD, 8 MUD and 4 mMUD • 10 Flu/Mel/Alemtuzumab and 6 Flu/Treo/ Alemtuzumab Blood Advances, 2018

3. Results • 12/16 (75%) patients achieved CR; • 2/16 patients died of transplant related toxicity. • 9/15 FULL donor chimerism – 1 relapse, 1 PR • 5/15 MIXED chimerism – 1 PR • 1/15 AUTOLOGOUS reconstitution – CR

4. LTFU UPDATED COHORT N. centers 9 N. patients 31 Period 2007 - 2022 Type of JIA • Polyarthritis • sJIA 7 24 Median lines of IS 5 Median age at transplant (years) 9.5 (2-18) Complications associated with sJIA • MAS • ILD 19 5 Median follow-up (years) 6 (1-15)

5. HSCT CHARACTERISTICS HLA matching 10/10 MSD 6/31 (19%) 10/10 MUD 18/31 (58%) 9/10 MMUD 5/31 (16%) PTCy Haploidentical 2/31 (6%) Source of Stem Cell PBSCT 14 BM 17 Conditioning Flu/Mel/Alemtuzumab 10/31 Flu/Treo/Alemtuzumab 13/31 Other 8/31

6. LONG TERM RESULTS N=31 24/26 CR 1/26 PR 5/31 Died 14/31 CR 1/2 Relapsed / Active disease 1 patient – M: 0%, T <10%, B: 0%, CR 7 y post HSCT 5/1 2 CR 6/12 Active disea se 11/31 Relapse

7. CAUSES OF DEATH 1 Fungal chest infection D+85 1 RSV pneumonitis D+28 2 Thrombotic microangiopathy both 6/8 m post HSCT 1 Sepsis post-surgery for hips replacement 1.5 y, CR

8. RELAPSE/REMISSION Patient JIA subtype Time to relapse Type of relapse Chimerism at relapse Treatment at relapse Status at last FU Last FU Pt 1 Poly-JIA 1.6 y MAS WB:86%, M:92%, T: 56%, B: 76% Steroids Well, off IS 8.5 y Pt 14 sJIA + MAS 2.9 y Arthritis 100% MTX (for 6m) Well, off IS 8 y Pt 21 sJIA + MAS 2 m MAS 100% CsA Well, off IS 5 y Pt 22 sJIA + MAS 5 m MAS T: 75% M:83% CSA/steroids Well, off IS 4.8 y Pt 23 sJIA + MAS 1 m/1.5y MAS/ Arthritis T:96% M:99% / T:98% M:96% Infliximab/ IVIG/steroids/ ia steroids Well, off IS 8.7 y Pt 24 Poly-JIA + MAS 6 m MAS WB:15% 2nd graft, CR Well, off IS 2.4 y

9. RELAPSE/ ACTIVE DISEASE Patient JIA subtype Time to relapse Type of relapse Chimerism at relapse Treatment at relapse Last FU Pt 2 sJIA + MAS 10 y Arthritis WB:85% T: 100% M:82% MTX 15 y Pt 6 Poly – JIA 6 y Polyarthritis and then uveitis 100% Toc, Steroid injections, MMF, Certolizumab 9 y Pt 8 sJIA 3 y Polyarthritis T 67% B 30% M 10% Toc, Adalimumab, Abatacept, Tofacitinib 8 y Pt 9 sJIA 3 y Polyarthritis T 88% B 94% M 94% Etanercept, MTX, Golimumab 6 y Pt 10 sJIA 6 m Polyarthritis then MAS T 75% M 87% MTX, steroids, Adalimumab, Anakinra, Toc, Ruxolitinib, Joint injections 6.5 y Pt 15 sJIA + MAS 6 m Arthritis 100% Tofacitinib and prednisolone 1 y Pt 17 Poly – JIA 8 y Arthritis 100% Pred, siro, MTX, Canakinumab 8 y

10. Survival Outcomes 6y OS: 84% • Deaths within first 18 m CR: 19/26 (61%) at last FU PR: 1/26 (4%) O(S Relapse: 42% (11/26) • Achieved further CR: 5/11 (45%) • Active disease: 6/11 (54%) Deaths: 4x transplant related 1x complication post surgery, in CR No JIA related deaths

11. In summary •Allogeneic HSCT is an alternative option for patients with refractory and/or complicated sJIA; •Promising results for ILD; •Indications and Timing for transplant;

12. Future perspectives • Consensus Statement on indications and timing for transplant • Prospective study • Standardised transplant recommendations; • Consolidate response with biologics; • Biomarkers analysis to assess disease response • Short and LTFU including joint/quality of life assessments; • CAR T cells

13. Acknowledgements Teaching Hospital Motol, Prague Petr Sedlacek Renata Formankova GOSH Persis Amrolia Kanchan Rao Robert Chiesa Giovanna Lucchini Khushnuma Mullafironze Harini Rao Archana Rauthan Rheumatology Team GOSH Great North Children’s Hospital Andrew Gennery Mary Slatter Sophie Hambleton Terence Flood Zohreh Nademi Mario Abinun Andrew Cant Mark Friswell UCLH Rachael Hough Ben Carpenter Vicky Grandage Cincinnati Children’s Hospital Rebecca Marsh Sharat Chandra University of Children’s Hospital, Zurich, Switzerland Tayfun Güngör Ulrike Zeilhofer Necker Enfants Malades, University Hospital Paris, France Bénédicte Neven Despina Moshous Benjamin Fournier Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, USA Susan Prockop