Table 2.
Overview of the literature on immunomodulation in classic infantile Pompe patients after antibodies have formed
| Study | Pt | CRIM | Age at start of ERT | Age at start of IM | IM protocol | IM duration | Current ERT dosea | Follow-up since start of IM | Alive | Vent. free | Walks at study end | Titer at start of IM | Number of RTX infusions | B-cell recovery | Last known titer (time since B-cell recovery) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Messinger 2012 [19] | 1 | Neg | 7 w | 0.5 y | 1 | 40 m | 20 eow | 4.6 y | Yes | No | No | 1:1600 | 15 | Yes | 0 (20 m) |
| 2 | Neg | 16 d | 2 m | 1 | IVIG ongoing | 40 w | 3 y | Yes | Yes | Yes | 1:12,800 | 14 | Yes | 0 (10 m) | |
| Banugaria 2012 [25] | 1 | Neg | 4.2 m | 8.8 m | 2 | RTX twice | variable | 2.5 y | No | No | No | 1:25,600 | 6 | No | 1:102,400 (before recovery) |
| Markic 2013 [27] | 1 | Pos | 5 m | 17.5 m | 1 | 46 w | 20 eow | 3 y | Yes | No | No | 1:6400 | 7 | Yes | 0 (unknown) |
| Deodato 2013 [26] | 1 | Neg | 7 m | 13 m | 3 | 3 w | 20 eow | 22 m | Yes | No | No | 1:3200c | 1 | Yes | 1:100 (16 m) |
| Stenger 2015 [20] | 1 | Pos | 23 d | 11 m | 4 | Ongoing | 20 eow | 13 m | Yes | No | No | 1:204,800 | 11 | No | 1:1200 (no recovery) |
| Kazi 2016 [28] | 1 | Pos | 6.0 m | 2.4 y | 5A | 3 y | 40 w | 5.5 y | Yes | No | No | 1:204,800 | 19 | Yes | 0 (2.5 y) |
| 2 | Neg | 4.2 m | 2 y | 5B | Ongoing | 40 eow | 6.9 y | Yes | No | No | 1:819,200 | 52 | Yes | 0 (4 w) | |
| This study | 1 | Pos | 2.4 m | 6.6 y | 6 | Rap/IVIG ongoing | 40 w | 2.5 y | Yes | Yes | Nob | 1:156,250 | 3 | No | 1:31,250 (before recovery) |
| 2 | Neg | 5.8 m | 3.5 y | 6 | Rap/IVIG ongoing | 40 w | 2.1 y | Yes | Yes | Yes | 1:156,250d | 3 | Yes | 1:31,250 (2 y) | |
| 3 | Neg | 1.9 m | 2.3 y | 6 | Rap/IVIG ongoing | 40 w | 1.5 y | Yes | Yes | Yes | 1:781,250 | 3 | Yes | 1:156,250 (1.5 y) |
aExcluding Banugaria 2012 (one patient) and the patients in our study, all patients started ERT dosed at 20 mg/kg every other week
bPatient did learn to walk, but lost the ability at the age of 6 years
cTiter was previously 1:25,400
dTiter was previously 1:800,000
Pt Patient, CRIM cross-reactive immunologic material, Pos Positive, Neg Negative, ERT enzyme replacement therapy, w weeks, m months, y years, IM immunomodulation, eow every other week, RTX Rituximab, Vent. free ventilator-free survival, MTX Methotrexate, IVIG intravenous immunoglobulin, Rap Rapamycin
Immunomodulation (IM) protocol used per study:
1. RTX 375 mg/m2/dose for 4 weekly iv doses followed by maintenance doses; MTX 0.5 mg/kg weekly oral doses; IVIG 500 mg/kg/month.
2. Cyclophosphamide 15 mg/kg iv on day 1 followed by 2 mg/kg/day iv for 9 days, IVIG 400 mg/kg day 5 through 9; Plasmapheresis day 1, 3 and 5 in week 20, 34 and 56. Between week 34 and 56 oral Cyclophosphamide 2 mg/kg was given. Followed by iv RTX 375 mg/m2/week in weeks 99 through 102 and in weeks 140 and 141.
3. Plasmapheresis on days 1, 3 and 5. RTX 375 mg/m2 iv once on day 7, directly followed by IVIG (dose not mentioned), with 4 extra IVIG doses over the following 8 months.
4. RTX 375 mg/m2/dose iv followed by 10 maintenance doses; Bortezomib 1 .3mg/m2/dose in 2 sessions of 4 iv doses. MTX 0.5 mg/kg for 27 oral doses; IVIG 500 mg/kg for 5 doses.
5. A Cyclophosphamide 250 mg/m2 iv twice; RTX 375 mg/m2/dose in 2 sessions of 4 doses followed by 11 maintenance doses; Bortezomib 1 .3mg/m2/dose in 3 sessions of 4 iv doses; MTX 15 mg/m2 oral doses; IVIG 400-500 mg/kg/month B RTX 375 mg/m2/dose for 4 iv doses followed by RTX maintenance doses 70 weeks later; Bortezomib 1 .3mg/m2/dose in 4 sessions of 4 iv doses; MTX 15 mg/m2 oral doses; IVIG 400-500 mg/kg/month.
6. RTX 375 mg/m2/dose for 3 iv doses; Bortezomib 1 .3mg/m2/dose for 6 iv doses. Rapamycin daily according to body weight from week 4 onwards; IVIG 500 mg/kg/month.