Abstract
Abstract 1174
Inhibitors are the most serious complication of hemophilia A (HA) treatment. Current optimal intervention for inhibitor eradication is immune tolerance induction (ITI), the goal of which is for the patient to resume therapy with FVIII. Basic and clinical research have strongly supported that VWF containing FVIII concentrates may be less immunogenic and are effective in primary ITI as well as for rescue ITI for those who fail to develop tolerance with recombinant proteins.
To assess the outcome of rescue and primary ITI in children (<18 years old) and adults with a single FVIII/VWF product (Fanhdi®, Grifols, Barcelona, Spain).
Retrospective data from HA patients (FVIII< 2%) with inhibitors from 22 centers in Spain, Italy and Germany, who underwent primary or rescue ITI with FVIII/VWF concentrate were evaluated. Success, partial success and failure were defined based on the criteria of the consensus recommendations of the 2006 International ITI Workshop.
The largest international multicenter study on ITI using a single product has evaluated 41 cases of primary ITI (32 children and 9 adults) and 19 cases of rescue ITI (17 children and 2 adults).
illustrates the overall response rates for children and adults.
| Table 1 . | Primary ITI . | Rescue ITI . |
|---|---|---|
| Children (n = 49) | Complete Success = 21 (65%) | Complete Success = 6 (35%) |
| Primary ITI – n = 32 (65%) | Partial Success = 7 (22%) | Partial Success = 6 (35%) |
| Rescue ITI – n = 17 (35%) | Failure = 4 (13%) | Failure = 5 (30%) |
| Adults (n = 11) | Complete Success = 5 (56%) | Complete Success = 1 (50%) |
| Primary ITI – n = 9 (82%) | Partial Success = 3 (33%) | Partial Success = 1 (50%) |
| Rescue ITI – n = 2 (18%) | Failure = 1 (11%) | Failure = 0 |
| Table 1 . | Primary ITI . | Rescue ITI . |
|---|---|---|
| Children (n = 49) | Complete Success = 21 (65%) | Complete Success = 6 (35%) |
| Primary ITI – n = 32 (65%) | Partial Success = 7 (22%) | Partial Success = 6 (35%) |
| Rescue ITI – n = 17 (35%) | Failure = 4 (13%) | Failure = 5 (30%) |
| Adults (n = 11) | Complete Success = 5 (56%) | Complete Success = 1 (50%) |
| Primary ITI – n = 9 (82%) | Partial Success = 3 (33%) | Partial Success = 1 (50%) |
| Rescue ITI – n = 2 (18%) | Failure = 1 (11%) | Failure = 0 |
describes the rescue and primary ITI outcome for high risk patients. Risk factors for poor response include: failure of a previous ITI, inhibitor peak >200 BU, age at ITI start >7 years old, titer ≥ 10 BU at ITI start and >24 months between diagnosis and start of ITI.
| Table 2 . | Number of risk factors . | 0 . | 1 . | 2 . | 3 . | 4 . | 5 . |
|---|---|---|---|---|---|---|---|
| Primary ITI (n=41) | Complete success | 12 | 7* | 2 | 4 | 1 | 0 |
| Partial success | 2 | 1 | 2 | 3 | 1 | 0 | |
| Failure | 0 | 4* | 2 | 0 | 0 | 0 | |
| Rescue ITI (n=19) | Complete success | 0 | 0 | 0 | 4 | 3 | 0 |
| Partial success | 0 | 0 | 1 | 3* | 1 | 2 | |
| Failure | 0 | 1 | 1 | 1 | 1 | 1 |
| Table 2 . | Number of risk factors . | 0 . | 1 . | 2 . | 3 . | 4 . | 5 . |
|---|---|---|---|---|---|---|---|
| Primary ITI (n=41) | Complete success | 12 | 7* | 2 | 4 | 1 | 0 |
| Partial success | 2 | 1 | 2 | 3 | 1 | 0 | |
| Failure | 0 | 4* | 2 | 0 | 0 | 0 | |
| Rescue ITI (n=19) | Complete success | 0 | 0 | 0 | 4 | 3 | 0 |
| Partial success | 0 | 0 | 1 | 3* | 1 | 2 | |
| Failure | 0 | 1 | 1 | 1 | 1 | 1 |
Time from diagnosis to ITI start not available in 1 patient (this risk factor is not considered in that patient).
The response rate of 87% (CS+PS) in primary ITI exceeds that previously reported with any product class. The response rate (CS+PS) of 74% in the higher risk profile of rescue ITI is what one might expect for primary ITI. These excellent results, using a single VWF containing FVIII product, should encourage the use of this class of product for immune tolerance.
The authors acknowledge Grifols financial support of the study. The authors also acknowledge Drs Jeffrey Spears and Roser Peiro, Grifols, for their editorial assistance in preparation of the abstract.
Aledort:Grifols: Advisory Board Other, Honoraria; Kedrion: Advisory Board, Advisory Board Other; Baxter: DSMB, DSMB Other; Octapharma: DSMB, DSMB Other. Off Label Use: This FVIII is not licensed for ITI - nor is any other product. Oldenburg:d and e: Baxter, Bayer, Biotest, CSL-Behring, Grifols, Inspiration, NovoNordisk, Octapharma, Pfizer e: Biogen IDec, Swedish Orphan Biovitrum: Honoraria, Research Funding. Santagostino:Bayer, Baxter, Pfizer, CSL Behring, Novo Nordisk, Biotest, Kedrion and Grifols: Speakers Bureau; Pfizer, Baxter, Bayer, CSL Behring, Kedrion, Grifols and Novo Nordisk: Consultancy; Novo Nordisk and Pfizer: Research Funding. Jimenez Yuste:Grifols, Baxter, Pfizer, NovoNordisk: Advisory Board Other, Consultancy.
Author notes
Asterisk with author names denotes non-ASH members.
