Table 2.
Immunological reconstitution after CART19 loss.
| Patient 1 | Patient 2 | Patient 3 | |
|---|---|---|---|
| Gender | Female | Male | Female |
| Age (years) | 4.4 | 18 | 6.7 |
| Age at ALL diagnosis | 5 months | 12 years | 2 years |
| Previous HSCT | Yes (11 mo) HSCT with MUD 10/10. PTLD (14 mo) with rtx treatment and low grade chronic cutaneous and gut GVHD | Yes (15.87 yo) HSCT with MRD 10/10. Reduced intensity conditioning regimen | Yes (4 yo). HSCT with MUD 10/10. Conditioning regimen: total corporal irradiation tiotepa and cyclophosphamide |
| Number of ALL relapses | One | Two | Three |
| Prior ALL lines of therapyb | One line with HSCT after complete remission | Three lines | Four lines |
| CART19 protocol | CAR T-Novartis® (CTL019-B2202) | CAR T-Novartis® (CCTL019B2001X) | CART ARI0001 |
| CAR T-cell infusion dose | 4 × 106/kg CTL019 | 1.7 × 106/kg CTL019 | 1st infusion: 5 × 106/kg ARI-0001 2nd infusionb: 2 × 106/kg ARI-0001 |
| B-cell aplasia duration (months) | 12.2 | 2.13 | 9.8 |
| Immunology evaluation at last follow-up visit | |||
| Date of last evaluation after CART19 loss (months) | 27 | 22.5 | 9 |
| Immunoglobulin levels | |||
| IgG (g/L) | 8.66 (6.64–13.7)a | 6.77 (6.50–15) | 12.6 (6.64–13.7)a |
| IgM (g/L) | 0.27 (0.45–1.96) | 0.56 (0.40–3.45) | 0.61 (0.45–1.96) |
| IgA (g/L) | <0.01 (0.35–1.91) | 1.61 (0.76–3.90) | <0.01 (0.35–1.91) |
| Total B-cell counts (%/abs) | 23%/299 (13–27%/270–860) | 26%/468 (6–23%/110–570) | 24%/216 (13–27%/270–860) |
| Naïve B-cell counts (%/abs) | 98%/258.7 (62–94/70–630) | 91.4%/427.75 (33–95%/28–550) | 96.7%/208.8 (62–94%/70–630) |
| Memory CD27+ B cells | 0.9%/2.37 (3–18%/7–51) | 8.6%/40.24 (5–60%/4.5–130) | 1.3%/2.8 (3–18%/7–51) |
| Total T-cell count (%/abs) | 69%/897 (60–76%/1300–2600) | 69%/1242 (56–84%/1000–2200) | 68%/612 (60–76%/1200–2600) |
| TL CD4+ | 42%/546 (31–47%/650–1500) | 34%/612 (31–52%/530–1300) | 26%/234 (31–47%/650–1500) |
| TL CD8+ | 24%/312 (18–35%/370–1200) | 32%/576 (18–35%/330–920) | 41%/369 (18–35%/370–1200) |
| Proliferative responses to mitogens | normal | normal | normal |
| S. tiphy antibody responses (U/ml)b | Basal: 9.8 Post vaccine: 8.9 | Not performed | Not performed |
| Current status | Free of disease. No HSCT | ALL relapse after 22 months free of disease | HSCT due to myelodysplasia |
ALL acute lymphoblastic leukaemia, CART19 CD19-Chimeric antigen receptor, HSCT haematopoietic stem cell transplant, PTLD post-transplant lymphoproliferative disease, MUD matched unrelated donor, MRD matched related donor, rtx rituximab, GVHD graft-versus-host disease, CTL cytotoxic T lymphocyte, TL T lymphocyte.
aUnder IgRT **Protective levels 32 U/mL.
bA line of therapy consists of ≥1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens.